Benzylamine → (3aR,4R,5S,7aS)-2-benzyl-5-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(4-fluorophenyl)octahydro-1H-isoindole

HRID 1393323노트

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HRID 1393323 반응식
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@@H:19]([CH2:22]CS([O-])(=O)=O)[C@@H:18]([CH2:28]CS([O-])(=O)=O)[C@@H:17]2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(O)C>[CH2:43]([N:50]1[CH2:28][C@@H:18]2[C@H:19]([CH2:20][CH2:21][C@H:16]([O:15][C@@H:13]([C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:42])([F:41])[F:1])[CH:4]=3)[CH3:14])[C@H:17]2[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:22]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

참가 물질

4

반응물 2

HCID 7504BenzylamineHCID 86613573[(1S,2R,3R,4S)-4-{(1R)-1-[3,5-bis(Trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-diyl]di(methylene)dimethanesulfonate

생성물 1

HCID 42639648(3aR,4R,5S,7aS)-2-benzyl-5-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(4-fluorophenyl)octahydro-1H-isoindole

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
150 °C

실험 절차

In a pressure tube was placed a solution of crude [(1S,2R,3R,4S)-4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-diyl]di(methylene) dimethanesulfonate (step H) in ˜20 mL ethanol and 1.2 mL (˜3 equiv.) benzylamine. The pressure tube was sealed and heated at 150° C. in an oil bath for 3 hr. The tube was cooled to RT and opened. The resulting mixture was transferred to a round bottom flask and the solvent removed under vacuum. The residue was diluted with 100 mL EtOAc, washed with 20 mL 5N aq. NaOH, dried over MgSO4 drying agent, filtered and the solvent was evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc to give 1.6 g of the title compound. 1H-NMR (CDCl3): δ: 7.35-7.20 (5 H, m), 7.50 (2 H, s), 6.97 (2 H, m), 6.85 (2 H, t, J=8.2 Hz), 4.42 (1 H, t, J=6.0 Hz), 3.75 (2 H, d, J=13.4 Hz), 3.50 (2 H, d, J=13.4 Hz), 3.30 (1 H, m), 2.96 (1 H, m), 2.52 (3 H, m), 2.19 (2 H, m), 1.98 (1 H, m), 1.97 (1 H, m), 1.86 (2 H, m), 1.57 (1 H, m), 1.33 (3 H, t, J=6.0 Hz), 1.30 (1 H, m). MS: (MH)+ 566.0.

후처리

  1. customIn a pressure tube was placed
  2. customThe pressure tube was sealed
  3. temperatureThe tube was cooled to RT
  4. customThe resulting mixture was transferred to a round bottom flask
  5. customthe solvent removed under vacuum
  6. additionThe residue was diluted with 100 mL EtOAc
  7. washwashed with 20 mL 5N aq. NaOH
  8. dry with materialdried over MgSO4 drying agent
  9. filtrationfiltered
  10. customthe solvent was evaporated under vacuum
  11. customThe residue was purified by flash column chromatography on silica gel eluting with EtOAc

출처 및 근거

ORD 기록
ord-827967d22f1340d0a522ce771c1267f9
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07345083B2

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