Acetic Acid → HCID 72548393, 화합물

HRID 2206432노트

반응식

HRID 2206432 반응식
Br.C(O)(=O)C.[Cl:6][C:7]1[C:8]([F:55])=[C:9]([C@@H:13]2[C@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[C@H:16]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[NH:15][C@H:14]2[C:33]([NH:35][C:36]2[CH:52]=[CH:51][C:39]([C:40]([O:42][CH2:43][C:44]([O:46]C(C)(C)C)=[O:45])=[O:41])=[CH:38][C:37]=2[O:53][CH3:54])=[O:34])[CH:10]=[CH:11][CH:12]=1>>[C:44]([CH2:43][O:42][C:40](=[O:41])[C:39]1[CH:51]=[CH:52][C:36]([NH:35][C:33]([C@H:14]2[C@H:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[C:8]=3[F:55])[C@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[C@H:16]([CH2:28][C:29]([CH3:31])([CH3:32])[CH3:30])[NH:15]2)=[O:34])=[C:37]([O:53][CH3:54])[CH:38]=1)([OH:46])=[O:45]

참가 물질

4

반응물 3

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 867040842-tert-butoxy-2-oxoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate

생성물 1

HCID 72548393HCID 72548393, 화합물

반응 조건

온도
0 °C

실험 절차

In a 25 mL round-bottomed flask, 45% hydrogen bromide in acetic acid (10 mL, 794 μmol) was added. It was cooled down to 0° C., then 2-tert-butoxy-2-oxoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (580 mg, 794 μmol) was added as solid. After 30 min, the reaction mixture was concentrated, and water (50 mL) was added to the residue. It was extracted with methylene chloride (2×300 mL). The methylene chloride layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product, which was purified by filtering through a short plug of silica gel to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid carboxymethyl ester as an off white solid (530 mg, 99% yield). LCMS (ES+) m/z calcd. for C33H32Cl2F2N3O6 [(M+H)+]: 674. found: 674.

후처리

  1. concentrationthe reaction mixture was concentrated
  2. additionwater (50 mL) was added to the residue
  3. extractionIt was extracted with methylene chloride (2×300 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas purified
  9. filtrationby filtering through a short plug of silica gel

출처 및 근거

ORD 기록
ord-cfb1e3c1711b4d14bbd82cdf24e8a297
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371280B2

반응 노트

불러오는 중…