2-脱氧-2,2-二氟戊呋喃糖-1-酮 3,5-二安息香酸盐 | 122111-01-7

• 物质功能分类: 生物化工 - 糖类化合物 - 单糖
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-脱氧-2,2-二氟戊呋喃糖-1-酮 3,5-二安息香酸盐
• 中文别名: 2-脱氧-2,2-二氟戊呋喃糖-1-酮3,5-二安息香酸盐；2-脱氧-2,2-二氟-D-赤型-1-呋喃酮糖-3,5-二苯甲酰酯；核酮糖；2-脱氧-2,2-二氟-D-赤型-戊糖酸-3,5-二苯甲酸-γ-内酯；2-脱氧-2,2-二氟戊呋喃糖-1-酮-3,5-二安息香酸盐；2-脱氧-2,2-二氟戊呋喃糖-1-酮3.5-二安息香酸盐；2-脱氧-2,2-二氟-3,5-二苯甲酰氧基呋喃内酯；2-脱氧－2,2-二氟-D-赤型－呋喃戊糖-1-酮-3,5-二苯甲酸酯；3,5-二-O-苯甲酰基-2-脱氧-2,2-二氟-D-戊烷-1,4-内酯；2-脱氧-2,2-二氟-1-酮基-3,5-二苯甲酰基-D-核糖；2-脱氧-2,2-二氟-D-核糖-1-酮基-3,5-二苯甲酸酯；2-脱氧-2,2-二氟戊呋喃糖-1-酮-3,5-二苯甲酸酯；2-脱氧-2,2-二氟戊呋喃糖-1-酮-3,5-二安息香酸酯；吉西他滨中间体；(D-赤型,d-苏型)-2-脱氧-2,2-二氟戊呋喃糖-1酮 3,5-二安息香酸盐；2-脱氧-2,2-二氟-戊呋喃糖-1-酮-3,5-二苯甲酸酯；2-脱氧-2,2-二氟-D-赤式-1-呋喃酮糖-3,5-二苯甲酸酯
• 英文名称: 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate
• 英文别名: 3,5-di-O-benzoyl-2,2-deoxy-2,2-difluoro-D-arabinofuran-1-one；2-deoxy-2,2-difluoro-D-erythro-1-furanose-3,5-dibenzoyl ester；2-deoxy-2,2-difluoro-D-erythro-1-furanosulose-3,5-dibenzoyl ester；2-deoxy-2,2-difluoro-D-erythro-pentonic acid γ-lactone 3,5-dibenzoate；2¹-deoxy-2¹,2¹-difluoro-3,5-di-O-benzoyl-1-oxoribose；2-deoxy-D-erythro-2,2-difluoro-pentafuranos-1-ulose-3,5-dibenzoate；2-deoxy-2,2-difluoro-D-pentofuranose-1-ketone-3,5-dibenzoate；2-deoxy-3,5-di-O-benzoyl-2,2-difluororibonolactone；2-deoxy-2,2-difluoro-3,5-dibenzoate-1-oxoribose；2-deoxy-2,2-difluoro-D-erythro-pentafuranos-1-ulose-3,5-dibenzoate；2-deoxy-2,2-difluoro-D-erythropentofurano-1-ulose-3,5-dibenzoate；((2R,3R)-3-(Benzoyloxy)-4,4-difluoro-5-oxotetrahydrofuran-2-yl)methyl benzoate；[(2R,3R)-3-benzoyloxy-4,4-difluoro-5-oxooxolan-2-yl]methyl benzoate
• CAS: 122111-01-7
• 化学式: C₁₉H₁₄F₂O₆
• 分子量: 376.313
• InChiKey: SHHNEUNVMZNOID-HUUCEWRRSA-N

物化性质

• 熔点：
  117-119 °C(lit.)
• 沸点：
  437.2±45.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  -20°C 冰箱

SDS

2-Deoxy-2,2-difluoro-D-erythro-pentonic Acid γ-Lactone Revision number: 5
3,5-Dibenzoate
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
2-Deoxy-2,2-difluoro-D-erythro-pentonic Acid γ-Lactone 3,5-Dibenzoate
Product name:


Revision number: 5

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
Not classified
PHYSICAL HAZARDS
HEALTH HAZARDS Not classified
Not classified
ENVIRONMENTAL HAZARDS
GHS label elements, including precautionary statements
None
Pictograms or hazard symbols
Signal word No signal word
None
Hazard statements
Precautionary statements: None

---

Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: 2-Deoxy-2,2-difluoro-D-erythro-pentonic Acid γ-Lactone 3,5-Dibenzoate
Percent: >98.0%(LC)
CAS Number: 122111-01-7
Chemical Formula: C19H14F2O6

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Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Get medical advice/attention if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth.
Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air-
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
Lactone 3,5-Dibenzoate

---

Section 5. FIRE-FIGHTING MEASURES
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
When extinguishing fire, be sure to wear personal protective equipment.
Special protective
equipment for firefighters:

---

Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, Use personal protective equipment. Keep people away from and upwind of spill/leak.
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment.
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a freezer.
Store away from incompatible materials such as oxidizing agents.
Heat-sensitive
Packaging material: Comply with laws.

---

Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Engineering controls: Install a closed system or local exhaust as possible so that workers should not be
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Hand protection: Protective gloves.
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Form: Crystal- Powder
Colour: White - Almost white
Odour: No data available
pH: No data available
Melting point/freezing point:123°C
Boiling point/range: No data available
Flash point: No data available
Flammability or explosive
limits:
No data available
Lower:
Upper: No data available
No data available
Relative density:
Solubility(ies):
[Water] No data available
[Other solvents]
Soluble: Dimethylformamide(DMF)
Lactone 3,5-Dibenzoate

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Hydrogen fluoride
products:

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Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
NTP = No data available
Reproductive toxicity: No data available

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
No data available
Fish:
Crustacea: No data available
No data available
Algae:
Persistence / degradability: No data available
No data available
Bioaccumulative
potential(BCF):
Mobility in soil
Log Pow: No data available
No data available
Soil adsorption (Koc):
Henry's Law No data available
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.

---

Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
Not listed
UN-No:

---

Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.
Lactone 3,5-Dibenzoate

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

2,2-二氟-3-脱氧-2,2-二氟戊呋喃糖-1-酮 3,5-二安息香酸盐是合成盐酸吉西他滨的中间体。盐酸吉西他滨是一种人工合成的新型二氟核苷类抗代谢抗肿瘤药物，最初由美国Eli Lilly公司开发并以商品名“健择”上市。

用途：该化合物用作制备盐酸吉西他滨的中间体。

反应信息

• 作为反应物：
  描述：

  2-脱氧-2,2-二氟戊呋喃糖-1-酮 3,5-二安息香酸盐 在 potassium tert-butylate 、 aluminum isopropoxide 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 1.5h， 生成 2-脱氧-2,2-二氟-3,5-二苯甲酰基-D-呋喃核糖
  参考文献：
  名称：

  一种吉西他滨中间体甲磺酰酯的制备方法

  摘要：

  本发明涉及一种吉西他滨中间体甲磺酰酯的制备方法，属于药物中间体合成技术领域。为了解决现有的方法转化率低和废液量大的问题，提供一种吉西他滨中间体甲磺酰酯的制备方法，该方法包括在非水溶性有机溶剂和催化量异丙醇混合的溶剂中，使式Ⅰ化合物2‑脱氧‑2,2‑二氟‑D‑赤型‑1‑呋喃酮糖‑3,5‑二苯甲酰酯在异丙醇铝和叔丁醇钠的共同存在下进行还原反应转化为式Ⅱ化合物；降温将反应液温度控制在5℃以下，加入甲基磺酰氯进行酯化反应，得到相应的式Ⅲ化合物吉西他滨中间体甲磺酰酯。本发明能够有效的提高反应的速度和转化率，减少了杂质的产生，具有较高的收率和纯度要求，且能够实现一锅法反应，简化了生产操作。

  公开号：

  CN109651459B
• 作为产物：
  描述：

  3-(2,2-二甲基-1,3-二氧戊环-4-基)-2,2-二氟-3-羟基丙酸乙酯 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 作用下， 以 水 为溶剂， 反应 8.0h， 生成 2-脱氧-2,2-二氟戊呋喃糖-1-酮 3,5-二安息香酸盐
  参考文献：
  名称：

  一种吉西他滨中间体的高选择性的合成方法

  摘要：

  本发明公开了一种吉西他滨中间体的高选择性的合成方法，具体包括如下工艺：具体包括如下工艺：Step1,T1的合成；Step2,T2的合成，将T1中滴加550kg双氧水，控制反应生成T2；Step3,T3的合成：向反应釜中加三水乙酸钠或者碳酸钠，用冰醋酸调节PH值，滴加10‑15％次氯酸钠水溶液，控制反应生成T3；Step4,T4的合成；Step5,T5的合成；Step6,T6的合成；Step7,T7的合成；Step8,T8的合成；Step9,T8构型转化；本吉西他滨中间体的高选择性的合成方法能够节省生产成本，同时还能够提高吉西他滨中间体的产率。

  公开号：

  CN112225767A

文献信息

• 一种2-脱氧-2,2-二氟戊呋喃糖-1-酮-3,5-二安息香酸盐的合成方法
  申请人：深圳市益鑫智能科技有限公司

  公开号：CN110845454A

  公开（公告）日：2020-02-28

  本发明以2,2‑二甲基‑4H‑1,3‑二氧环己烯‑4‑酮和二氟溴乙酸为反应原料，原料不必具有特定手性构型，在一价铜盐和手性配体作用下，选择性合成特定构型的环化产物，且反应收率高，反应条件较Reformatsky反应更加简单、温和、环境友好；然后在弱酸性条件下水解，避免了五元环内酯的水解，减少了副反应的发生；NaBH4‑I2还原体系能够选择性还原羧酸而对内酯不发生还原作用，还原收率高。本发明提供的2‑脱氧‑2,2‑二氟戊呋喃糖‑1‑酮‑3,5‑二安息香酸盐合成路线，操作简单、环境友好、总收率高，适于工业化生产，能够有效降低吉西他滨的生产成本。
• 吉西他滨关键中间体磺化糖的工业制备工艺
  申请人：连云港恒运药业有限公司

  公开号：CN106478747B

  公开（公告）日：2018-03-20

  本发明涉及式（I）化合物，即吉西他滨关键中间体磺化糖的制备方法，式（Ⅱ）化合物经硼氢化钠还原、羟基保护、拆分得最终产物。该方法工艺简单，产率高，产品纯度好，无需苛刻的反应条件，十分适合工业生产。（I）。
• 一种2-脱氧-2，2-二氟-D-赤型-呋喃戊糖-3， 5-二苯甲酸酯的制备方法
  申请人：江苏八巨药业有限公司

  公开号：CN109651460B

  公开（公告）日：2020-06-26

  本发明涉及一种2‑脱氧‑2，2‑二氟‑D‑赤型‑3，5‑二苯甲酸酯的制备方法，属于药物中间体合成技术领域。为了解决现有的选择性和安全性差的问题，提供一种2‑脱氧‑2，2‑二氟‑D‑赤型‑3，5‑二苯甲酸酯的制备方法，该方法包括使2‑脱氧‑2，2‑二氟‑D‑赤型‑1‑呋喃酮糖‑3，5‑二苯甲酰酯在硼氢化钠和PPO‑CBS固载催化剂的共同作用下进行催化还原反应转化为产物2‑脱氧‑2，2‑二氟‑D‑赤型‑3，5‑二苯甲酸酯。本发明具有高手性选择性的特性和提高整体的转化率，起到更好的不对称还原作用，实现α‑异构体纯度大于95％以上。
• Stereospecific Synthesis of 2-Deoxy-2,2-difluororibonolactone and Its Use in the Preparation of 2′-Deoxy-2′,2′-difluoro-β-D-ribofuranosyl Pyrimidine Nucleosides: The Key Role of Selective Crystallization
  作者：T. S. Chou、P. C. Heath、L. E. Patterson、L. M. Poteet、R. E. Lakin、A. H. Hunt

  DOI：10.1055/s-1992-26167

  日期：——

  A stereospecific synthesis of 2′-deoxy-2′,2′-difluorocytidine (gemcitabine), a potential anticancer agent, is described. The stereoselectivity was accomplished via two diastereoselective crystallizations, i. e. the crystallization of the key intermediate, difluororibonolactone 2a, and the crystallization of the hydrochloride salt of gemcitabine 16b from the anomeric mixture. Because of the availability of 2a in large quantities, other 2′-deoxy-2′,2′-difluoropyrimidine nucleosides such as 2′-deoxy-2′,2′-difluorouridine (19) were synthesized for structure-activity relationship studies.

  本文描述了潜在抗癌药物2′-脱氧-2′,2′-二氟胞苷（吉西他滨）的立体特异性合成。通过两次非对映选择性结晶实现了立体选择性：即关键中间体二氟乳糖内酯2a的结晶，以及从异头混合物中结晶出吉西他滨的盐酸盐16b。由于2a可以大量获得，因此合成了其他2′-脱氧-2′,2′-二氟嘧啶核苷，如2′-脱氧-2′,2′-二氟尿苷（19），用于结构-活性关系研究。
• Azido nucleosides and nucleotide analogs
  申请人：Alios BioPharma, Inc.

  公开号：US09346848B2

  公开（公告）日：2016-05-24

  Disclosed herein are 4′-azido-substituted nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of 4′-azido-substituted nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a 4′-azido-substituted nucleoside, a nucleotide and/or an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

  本文披露了4'-偶氮基取代核苷、核苷酸及其类似物，包括其中一个或多个4'-偶氮基取代核苷、核苷酸及其类似物的药物组合物，以及它们的合成方法。本文还披露了使用4'-偶氮基取代核苷、核苷酸和/或其类似物来改善和/或治疗疾病和/或病况的方法，包括由副粘病毒和/或正粘病毒引起的感染。病毒感染的例子包括呼吸道合胞病毒（RSV）和流感感染。