4-氨基-6-氟色满-4-羧酸 | 90477-46-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4-氨基-6-氟色满-4-羧酸
• 英文名称: (RS)-4-amino-6-fluorochroman-4-carboxylic acid
• 英文别名: 6-fluoro-4-aminochroman-4-carboxylic acid；4-amino-6-fluorochroman-4-carboxylic acid；4-amino-6-fluoro-2,3-dihydrochromene-4-carboxylic acid
• CAS: 90477-46-6
• 化学式: C₁₀H₁₀FNO₃
• 分子量: 211.193
• InChiKey: FATKFOJBJPZZED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基-6-氟色满-4-羧酸 在 sodium hypochlorite 作用下， 以 sodium hydroxide 为溶剂， 生成 6-fluoro-4-chloroiminochroman
  参考文献：
  名称：

  Sorbinil by optical resolution of precursor

  摘要：

  Sorbinil是通过S-6-氟-4-尿素基色烷-4-羧酸的环化得到的，而S-6-氟-4-尿素基色烷-4-羧酸则是通过用D-(+)-(1-苯乙基)胺或L-(-)-麻黄碱的对映体盐分离来分离外消旋的6-氟-4-尿素基色烷-4-羧酸而得到的。

  公开号：

  US04435578A1
• 作为产物：
  描述：

  2,3-dihydro-6-fluorospiro<4H-1-benzopyran-4,4'-2'-phenyloxazolidin>-5'-one 以60-85的产率得到4-氨基-6-氟色满-4-羧酸
  参考文献：
  名称：

  J. Org. Chem. 1987, 52, 3587-3591

  摘要：

  DOI：

文献信息

• Sorbinil by optical resolution of precursor
  申请人：Pfizer Inc.

  公开号：US04435578A1

  公开（公告）日：1984-03-06

  Sorbinil is obtained by cyclization of S-6-fluoro-4-ureidochromane-4-carboxylic acid, which is in turn obtained by resolution of racemic 6-fluoro-4-ureidochroman-4-carboxylic acid via diasteromeric salts with either D-(+)-(1-phenethyl)amine or L-(-)-ephedrine.

  Sorbinil是通过S-6-氟-4-尿素基色烷-4-羧酸的环化得到的，而S-6-氟-4-尿素基色烷-4-羧酸则是通过用D-(+)-(1-苯乙基)胺或L-(-)-麻黄碱的对映体盐分离来分离外消旋的6-氟-4-尿素基色烷-4-羧酸而得到的。
• Regeneration of 6-fluoro-4-chromanone from
  申请人：Pfizer Inc.

  公开号：US04551542A1

  公开（公告）日：1985-11-05

  6-Fluoro-4-chromanone can be regenerated from (R)-6-fluoro-4-ureidochroman-4-carboxylic acid, or from mixtures of (R)-6-fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification, by oxidation with a permanganate, especially potassium permanganate. 6-Fluoro-4-chromanone is a chemical intermediate useful for preparing sorbinil, an aldose reductase inhibitor which can be used in clinical medicine for the control of the chronic complications of diabetes. (R)-6-Fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification are by-products from the production of sorbinil from 6-fluoro-4-chromanone.

  6-氟-4-香豆酮可以通过过氧化钾，特别是高锰酸钾的氧化作用，从(R)-6-氟-4-尿素基香豆酸或(R)-6-氟-4-尿素基香豆酸和其外消旋异构体的混合物中再生。6-氟-4-香豆酮是一种化学中间体，用于制备索比尼尔，一种醛糖还原酶抑制剂，可用于临床医学中控制糖尿病的慢性并发症。(R)-6-氟-4-尿素基香豆酸及其外消旋异构体是从6-氟-4-香豆酮制备索比尼尔的副产物。
• Sorbinal by optical resolution of precursor 6-fluro-4-ureidochroman-4-carboxylic acid
  申请人：PFIZER INC.

  公开号：EP0109232A1

  公开（公告）日：1984-05-23

  Sorbinil is obtained by cyclization of S-6-fluoro-4-ureidoch- romane-4-carboxylic acid, wich is in turn obtained by resolution of racemic 6-fluoro-4-ureidochroman-4-carboxylic acid via dias- teromeric salts with either D-(+)-(1-phenethyl) amine or L-(-)-ephedrine.

  索比尼尔是由 S-6-氟-4-脲基-4-罗曼-4-羧酸环化而成，而 S-6-氟-4-脲基-4-罗曼-4-羧酸又是由外消旋 6-氟-4-脲基-4-罗曼-4-羧酸通过与 D-(+)-(1-苯乙基)胺或 L-(-)-麻黄碱的二异构盐解析而成。
• Regeneration of 6-fluoro-4-chromanone from by-products in the synthesis of sorbinil
  申请人：PFIZER INC.

  公开号：EP0111387A1

  公开（公告）日：1984-06-20

  6-Fluoro-4-chromanone, a sorbinil intermediate, is regenerated from enantiomeric and mixtures of enantiomeric and racemic compounds obtained as major by-products in the synthesis of sorbinil. The regenerated intermediate is useful in the synthesis of additional sorbinil.

  6-Fluoro-4-chromanone 是一种山梨醇中间体，可从合成山梨醇的主要副产品对映体和对映体混合物以及外消旋化合物中再生。 再生的中间体可用于合成更多的山梨醇。
• Process for the production as asymmetric hydantoins
  申请人：PFIZER INC.

  公开号：EP0172719A1

  公开（公告）日：1986-02-26

  An improved process for preparing (4S)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',S'-dione (sorbinil) or its (2R)-methyl derivative (2-methylsorbinil) is disclosed herein, starting from p-fluorophenol in each instance. The final products obtained have known pharmaceutical value as agents for the control of certain chronic diabetic complications. Key steps concerned with the process involve converting p-fluorophenol into the appropriate β-(4-fluorophenoxy)-alkane halide, followed by amidoalkylation with N-benzoyl or N-(lower alkanoyl)- a-hydroxyglycine to form an intermediate 2-amidoalkylated derivative thereof, and then dehydration and spiroalkylation of said intermediate by treatment with a dehydrating agent and a base to yield a spiroalkylated azlactone compound. The latter compound is then subsequently converted to the known 4-amino-6-fluorochroman-4-carboxylic acid or the novel (2R-methyl derivative thereof, both in the form of their hydrohalide acid addition salts, by employing acid hydrolysis and the intermediate spiro-amino acid hydrohalide salt is thereafter converted to the corresponding methyl or ethyl ester and resolved with a-chymotrypsin to afford the desired (S)-methyl or (S)-ethyl ester. Treatment of either of these latter two esters with an alkali metal cyanate in an acid medium then effects conversion of same to the desired spiro-hydantoin ring compound. Alternatively, the spiro-amino acid hydrohalide salt can also be converted to the desired spiro-hydantoin ring compound in a known manner, involving a sequence of three reaction steps. The spiroalkylated azlactone compound of the instant invention, as well as the methyl and ethyl esters mentioned above, are themselves novel compounds and are valuable as synthetic intermediates in the process of this invention.

  本文公开了一种制备(4S)-6-氟-螺-[色满-4,4'-咪唑烷]-2',S'-二酮（sorbinil）或其(2R)-甲基衍生物（2-甲基sorbinil）的改进工艺，每种工艺均从对氟苯酚开始。所获得的最终产品作为控制某些慢性糖尿病并发症的药物具有已知的药用价值。该工艺的关键步骤包括将对氟苯酚转化为适当的 β-（4-氟苯氧基）-卤代烷烃，然后用 N-苯甲酰基或 N-（低级烷酰基）-a-羟基甘氨酸进行氨基烷基化，形成其 2-氨基烷基化衍生物中间体，然后用脱水剂和碱对上述中间体进行脱水和螺烷基化处理，得到螺烷基化氮内酯化合物。然后通过酸水解将后一种化合物转化为已知的 4-氨基-6-氟二氢苯并吡喃-4-羧酸或其新型（2R-甲基）衍生物，二者均为氢卤酸加成盐形式，随后将中间体螺烷基氨基酸氢卤酸盐转化为相应的甲酯或乙酯，并用 a-胸腺胰蛋白酶溶解，得到所需的（S）-甲酯或（S）-乙酯。用碱金属氰酸酯在酸性介质中处理后两种酯中的任何一种，都会将其转化为所需的螺环海因环化合物。另外，螺烷基氨基酸氢卤化物盐也可以按照已知的方式转化为所需的螺海因环化合物，其中涉及三个反应步骤。本发明的螺烷基化氮内酯化合物以及上述的甲酯和乙酯本身就是新颖的化合物，在本发明的工艺中作为合成中间体是很有价值的。