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

HRID 1393323ノート

反応式

HRID 1393323 の反応式
[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

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
150 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-827967d22f1340d0a522ce771c1267f9
出典データセット
uspto-grants-2008_03
特許番号
US07345083B2

反応ノート

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