Toluene → (S)-6-Methyl-3-azabicyclo[3.2.0]heptane-1,3-dicarboxylic acid 3-benzyl ester 1-methyl ester

HRID 1917285노트

반응식

HRID 1917285 반응식
C[Si](C)(C)[N-][Si](C)(C)C.[K+].C1(C)C=CC=CC=1.[CH3:18][O:19][C:20]([CH:22]1[CH:26]([C@@H:27]([CH3:30])[CH2:28]I)[CH2:25][N:24]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH2:23]1)=[O:21].[Cl-].[NH4+]>O1CCCC1>[CH3:18][O:19][C:20]([C@@:22]12[CH2:28][CH:27]([CH3:30])[CH:26]1[CH2:25][N:24]([C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[CH2:23]2)=[O:21]

참가 물질

6

반응물 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 674908464-[(R)-2-iodo-1-(methyl)ethyl]pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester

생성물 1

HCID 67490834(S)-6-Methyl-3-azabicyclo[3.2.0]heptane-1,3-dicarboxylic acid 3-benzyl ester 1-methyl ester수율 91.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A 0.5 M solution of potassium hexamethyldisilazide in toluene (28 mL, 14.0 mmol) was added dropwise to a solution of 4-[(R)-2-iodo-1-(methyl)ethyl]pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester (5.0 g, 11.5 mmol) in anhydrous tetrahydrofuran (100 mL) in an argon atmosphere at −78° C. After completion of dropwise addition, the mixture was stirred at the same temperature for 30 minutes. An ammonium chloride solution was added, and the mixture was heated to room temperature. After extraction with ethyl acetate, drying over magnesium sulfate, and filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→7:3) to give 3.2 g (91%) of the diastereomer mixture title compound as a colorless oil. The diastereomers were used for the next step without separation.

후처리

  1. additionAfter completion of dropwise addition
  2. extractionAfter extraction with ethyl acetate
  3. dry with materialdrying over magnesium sulfate, and filtration
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→7:3)

출처 및 근거

ORD 기록
ord-67137c13da684c14a81434785bad0ecb
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618094B2

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