1,1'-Carbonyldiimidazole → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide

HRID 1516624노트

반응식

HRID 1516624 반응식
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31](O)=[O:32])[CH2:26]2)=[CH:21][CH:20]=1>O1CCCC1>[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31]([NH2:3])=[O:32])[CH2:26]2)=[CH:21][CH:20]=1

참가 물질

4

반응물 2

HCID 682631,1'-CarbonyldiimidazoleHCID 67409315(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

생성물 1

HCID 44128415(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide수율 96.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
18 °C

실험 절차

1,1′-carbonyldiimidazole (8.27 g, 51.0 mmol) was suspended and partly dissolved in tetrahydrofuran (110 mL) at 18° C. (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (14.0 g, 42.5 mmol; enantiomeric purity (S):(R)=99.5:0.5) was added as a solid together with tetrahydrofuran (30 mL) used for rinsing. The turbid solution, which turned into a white suspension after 15 min, was stirred 1 h at 16-20° C. and then transferred into a stirred 25% aqueous ammonia solution (7.95 mL) in tetrahydrofuran (80 mL). The last part of the white suspension was transferred with the aid of tetrahydrofuran (10 mL) for rinsing. After stirring for 0.5 h the reaction mixture was concentrated in vacuo to a volume of ˜70 mL and diluted with water (300 mL). Some ice was added to keep the temperature at 20-25° C. The white precipitate was collected by filtration, washed with water/tetrahydrofuran 80:20 and with heptane. Drying in vacuo at 20-45° C. afforded (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide (13.5 g, 96%) as a white solid. The purity of the material by HPLC was 96.9% (area) and the enantiomeric ratio (S):(R) was determined as 99.7:0.3.

후처리

  1. washfor rinsing
  2. washfor rinsing
  3. stirringAfter stirring for 0.5 h the reaction mixture
  4. concentrationwas concentrated in vacuo to a volume of ˜70 mL
  5. additiondiluted with water (300 mL)
  6. additionSome ice was added
  7. customat 20-25° C
  8. filtrationThe white precipitate was collected by filtration
  9. washwashed with water/tetrahydrofuran 80:20 and with heptane
  10. customDrying in vacuo at 20-45° C.

출처 및 근거

ORD 기록
ord-cdbd61a6a0ad400e92a51b2194a13bf3
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227505B2

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