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

HRID 1917285ノート

反応式

HRID 1917285 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-67137c13da684c14a81434785bad0ecb
出典データセット
uspto-grants-2013_12
特許番号
US08618094B2

反応ノート

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