methyl (4S)-amino-2,3-dihydro-6-fluoro-2(R)-methyl-4H-1-benzopyran-4-carboxylate | 103197-14-4

• 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
• 英文名称: methyl (4S)-amino-2,3-dihydro-6-fluoro-2(R)-methyl-4H-1-benzopyran-4-carboxylate
• 英文别名: methyl 4(S)-4-amino-6-fluoro-2(R)-methylchroman-4-carboxylate；methyl (2R,4S)-4-amino-6-fluoro-2-methyl-2,3-dihydrochromene-4-carboxylate
• CAS: 103197-14-4
• 化学式: C₁₂H₁₄FNO₃
• 分子量: 239.246
• InChiKey: BGIJXHNCUBTVDQ-KRTXAFLBSA-N

物化性质

• 沸点：
  326.8±42.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (4S)-amino-2,3-dihydro-6-fluoro-2(R)-methyl-4H-1-benzopyran-4-carboxylate 以54%的产率得到
  参考文献：
  名称：

  URBAN, FRANK J.

  摘要：

  DOI：
• 作为产物：
  描述：

  (R)-2-(4-fluorophenoxy)propanol 在 氯化亚砜 、 甲烷磺酸 、 溴 、 乙酸酐 、 potassium carbonate 、 三苯基膦 、 α-chymotrypsin 作用下， 以 盐酸 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 sodium chloride 为溶剂， 反应 80.0h， 生成 methyl (4S)-amino-2,3-dihydro-6-fluoro-2(R)-methyl-4H-1-benzopyran-4-carboxylate
  参考文献：
  名称：

  Novel synthesis of the aldose reductase inhibitor sorbinil via amidoalkylation, intramolecular oxazolidin-5-one alkylation and chymotrypsin resolution

  摘要：

  DOI：

  10.1021/jo00392a017

文献信息

• Spectral assignments for the aldose reductase inhibitor 4(S)-2,3-dihydro-6-fluoro-2(R)-methylspiro[chroman-4,4′-imidazoline]-2′,5′-dione and its synthetic intermediates
  作者：Mingan Wang、Manoj K. Mishra、Wenjun Zhu、Peter F. Kador

  DOI：10.1002/mrc.1697

  日期：2005.12

  The 1H and 13C NMR chemical shifts of the aldose reductase inhibitor 4(S)‐2,3‐dihydro‐6‐fluoro‐2(R)‐methylspiro[chroman‐4,4′‐imidazoline]‐2′,5′‐dione, methylsorbinil, and its seven synthetic intermediates, have been completely assigned on the basis of DEPT, COSY, g‐HSQC and g‐HMBC. All CF coupling constants from one‐bond to four‐bond in the 13C NMR spectra and HF and HH coupling constants from three‐bond

  醛糖还原酶抑制剂 4(S)-2,3-dihydro-6-fluoro-2(R)-methylspiro[chroman-4,4'-imidazoline]-2',5'-的 1H 和 13C NMR 化学位移二酮、甲基山梨醇及其七种合成中间体已完全基于 DEPT、COSY、g-HSQC 和 g-HMBC 进行分配。获得了13C NMR光谱中从单键到四键的所有CF耦合常数以及1H光谱中从三键到四键的HF和HH耦合常数。版权所有 © 2005 John Wiley & Sons, Ltd.
• 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。
• DIRLAM, NANCY L.;MOORE, B. S.;URBAN, F. J., J. ORG. CHEM., 52,(1987) N 16, 3587-3591
  作者：DIRLAM, NANCY L.、MOORE, B. S.、URBAN, F. J.

  DOI：——

  日期：——
• US4716113A
  申请人：——

  公开号：US4716113A

  公开（公告）日：1987-12-29
• US4841079A
  申请人：——

  公开号：US4841079A

  公开（公告）日：1989-06-20