Heptane → (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl ester

HRID 2357757ノート

反応式

HRID 2357757 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C@:9]2([OH:17])[O:14][CH2:13][C@@H:12]([CH3:15])[NH:11][C@H:10]2[CH3:16])[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:25]([O:27][CH2:28][Cl:29])=[O:26].CCCCCCC>ClCCl.O.C(OCC)(=O)C>[Cl:29][CH2:28][O:27][C:25]([N:11]1[C@H:12]([CH3:15])[CH2:13][O:14][C@:9]([C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=2)([OH:17])[C@@H:10]1[CH3:16])=[O:26]

参加物

8

反応物 4

HCID 8900HeptaneHCID 11430Potassium CarbonateHCID 60829ManifaxineHCID 62754Chloromethyl chloroformate

生成物 1

HCID 59613210(2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl ester収率 81.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
5 °C

実験手順

To a stirring solution of (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine (2.5 g, 10.28 mmol) in dichloromethane (50 mL) at room temperature under nitrogen, was added potassium carbonate (1.42 gm, 10.28 mmol). The mixture was cooled to 5° C. with a wet ice bath, and chloromethyl chloroformate (0.915 mL, 10.28 mmol) in dichloromethane (10 mL) was added dropwise. The mixture was allowed to warn to room temperature slowly and stirred over night. TLC analysis (1:1 heptane:ethyl acetate) indicated that the starting material was consumed and a new less polar spot had formed. Water was added to the mixture and then it was extracted with dichloromethane (3×). The organic layers were combined and dried over magnesium sulfate, filtered and the solvent was removed to afford a crude weight of 2.8 grams of (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl ester (1410) as an opaque tar.

後処理

  1. customto warn to room temperature
  2. customwas consumed
  3. customa new less polar spot had formed
  4. extractionit was extracted with dichloromethane (3×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed

出典と根拠

ORDレコード
ord-cfe0b918e9f8444ca14fdbe71722c72c
出典データセット
uspto-grants-2010_07
特許番号
US07763612B2

反応ノート

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