Sulfuric Acid → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

HRID 1807092노트

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HRID 1807092 반응식
C([O:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[C:11]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[CH:24]=2)([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])[NH:9]1)=[O:7])(C)(C)C.OS(O)(=O)=O>>[Cl:19][C:15]1[C:14]([F:20])=[C:13]([CH:12]2[C:11]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([F:30])[CH:24]=3)([C:21]#[N:22])[CH:10]([CH2:31][C:32]([CH3:34])([CH3:35])[CH3:33])[NH:9][CH:8]2[C:6]([OH:7])=[O:5])[CH:18]=[CH:17][CH:16]=1

참가 물질

3

반응물 2

HCID 1118Sulfuric AcidHCID 67296858rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

생성물 1

HCID 67299695rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid수율 98.1%

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온도
0 °C

실험 절차

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (0.6 g, 1.15 mmol) was cooled to 0° C., then conc. H2SO4 (2 mL) was added slowly. The reaction was stirred at RT for 2 hours. The mixture was then poured into ice and extracted with EtOAc. The organic phase was separated, dried over Na2SO4, filtered and solvent was removed under reduced pressure to yield a residue that was triturated with ethyl acetate/heptane and the precipitates were collected by filtration and washed with ether to yield the product rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-3-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (0.526 g, 98.1%) as a white solid. HRMS (ES+) m/z Calcd for C23H22Cl2F2N2O2S+H [(M+H)+]: 467.1099. found: 467.1097.

후처리

  1. additionThe mixture was then poured into ice
  2. extractionextracted with EtOAc
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customsolvent was removed under reduced pressure
  7. customto yield a residue that
  8. customwas triturated with ethyl acetate/heptane
  9. filtrationthe precipitates were collected by filtration
  10. washwashed with ether

출처 및 근거

ORD 기록
ord-29ce4bb4459247a39abad50227f249fc
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354444B2

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