Pyrrolidine → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1-pyrrolidin-1-ylpropyl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

HRID 505286노트

반응식

HRID 505286 반응식
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH:30](Br)[CH2:31][CH3:32])[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>CC#N.C(Cl)Cl.O>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH:30]([N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)[CH2:31][CH3:32])[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

6

반응물 2

HCID 31268PyrrolidineHCID 57617882(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-bromopropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

생성물 1

HCID 24896152(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1-pyrrolidin-1-ylpropyl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-bromopropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (67.1 mg, 0.106 mmol) in MeCN (200 μL) was added pyrrolidine (1 mL, 12.0 mmol). The reaction was stirred at room temperature for 16 hours and then purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA). The resulting solution was diluted with EtOAc (25 mL), washed with 1 M NaHCO3 (20 mL), extracted with EtOAc (25 mL), and washed with brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. To the residue was added 200 μL CDCl3, which resulted in a mixture that was diluted with CH2Cl2 (20 mL) and water (5 mL), and washed with 1 M NaOH solution (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1-pyrrolidin-1-ylpropyl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one. Rf=0.14 (25% EtOAc/hexanes). LCMS=583.3 (M+1)+. 1H NMR (CDCl3, 500 MHz, diastereomers present) δ 7.94 (s, 1H), 7.84 (s, 2H), 7.67-7.48 (m, 3H), 5.70-5.68 (m, 1H), 5.08-4.96 (m, 1H), 4.64-3.34 (m, 1H), 4.02-3.94 (m, 1H), 3.48-3.39 (m, 1H), 2.54-2.35 (m, 5H), 2.01-1.91 (m, 1H), 1.76-1.72 (m, 4H), 0.79-0.77 (m, 3H), 0.72-0.66 (m, 3H).

후처리

  1. custompurified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)
  2. additionThe resulting solution was diluted with EtOAc (25 mL)
  3. washwashed with 1 M NaHCO3 (20 mL)
  4. extractionextracted with EtOAc (25 mL)
  5. washwashed with brine (20 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionTo the residue was added 200 μL CDCl3, which
  10. customresulted in a mixture that
  11. washwashed with 1 M NaOH solution (5 mL)
  12. dry with materialThe organic layer was dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a8cfb37c1c48488086b9e57c160781e5
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781426B2

반응 노트

불러오는 중…