Cesium carbonate → (2S,4R)-Methyl 4-(2-chloro-4-((S)-1,1,1-trifluoropropan-2-yloxy)phenylsulfonyl)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)pyrrolidine-2-carboxylate

HRID 1025333노트

반응식

HRID 1025333 반응식
[Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][N:15]([C:17]([C:19]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20]2)=[O:18])[C@H:14]([C:29]([O:31][CH3:32])=[O:30])[CH2:13]1)(=[O:11])=[O:10].C(=O)([O-])[O-].[Cs+].[Cs+].[F:39][C:40]([F:45])([F:44])[C@H:41]([OH:43])[CH3:42]>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:43][C@@H:41]([CH3:42])[C:40]([F:45])([F:44])[F:39])[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][N:15]([C:17]([C:19]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:20][CH2:21]2)=[O:18])[C@H:14]([C:29]([O:31][CH3:32])=[O:30])[CH2:13]1)(=[O:10])=[O:11]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 6993809(2R)-1,1,1-trifluoropropan-2-olHCID 86762440(2S,4R)-methyl 4-(2-chloro-4-fluorophenylsulfonyl)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)pyrrolidine-2-carboxylate

생성물 1

HCID 86762439(2S,4R)-Methyl 4-(2-chloro-4-((S)-1,1,1-trifluoropropan-2-yloxy)phenylsulfonyl)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)pyrrolidine-2-carboxylate수율 90.5%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

Under an atmosphere of argon, (2S,4R)-methyl 4-(2-chloro-4-fluorophenylsulfonyl)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)pyrrolidine-2-carboxylate (200 mg, 331 μmol, Eq: 1.00, [prepared in analogy to General Procedure C, steps C1-C5, using 2-chloro-4-fluorothiophenol in step C2]) and cesium carbonate (194 mg, 595 μmol, Eq: 1.8) were combined with N,N-dimethylacetamide (2 ml) to give a colorless solution. (R)-1,1,1-trifluoropropan-2-ol (90.5 mg, 793 μmol, Eq: 2.4) was added. The reaction mixture was stirred over night at rt. The crude reaction mixture was concentrated in vacuo. The residue was poured into HCl (0.5 M, 5 ml) and extracted with ethyl acetate (5×20 ml). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 0% to 40% EtOAc in heptane) to yield the title compound as a white foam (178 mg, 67.1%, MS (m/e)=594.07 [M+H+])

후처리

  1. customto give a colorless solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. additionThe residue was poured into HCl (0.5 M, 5 ml)
  5. extractionextracted with ethyl acetate (5×20 ml)
  6. dry with materialThe organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 50 g, 0% to 40% EtOAc in heptane)

출처 및 근거

ORD 기록
ord-8b8f1a4af15a4ae3a2e9cd6947deb2de
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08729061B2

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