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

HRID 1351398Notes

Reaction equation

HRID 1351398 reaction equation
CS(O[CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([O:13][C@@H:14]([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[CH3:15])[C@@H:9]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C@@H:8]1[CH2:37]OS(C)(=O)=O)(=O)=O.[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[CH2:37][C@@H:8]2[C@H:7]([CH2:12][CH2:11][C@H:10]([O:13][C@@H:14]([C:16]3[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[C:18]([C:26]([F:28])([F:27])[F:29])[CH:17]=3)[CH3:15])[C@H:9]2[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH2:6]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 42639485HCID 42639485, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

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 seated 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 (5H, m), 7.50 (2H, s), 6.97 (2H, m), 6.85 (2H, t, J=8.2 Hz), 4.42 (1H, t, J=6.0 Hz), 3.75 (2H, d, J=13.4 Hz), 3.50 (2H, d, J=13.4 Hz), 3.30 (1H, m), 2.96 (1H, m), 2.52 (3H, m), 2.19 (2H, m), 1.98 (1H, m), 1.97 (1H, m), 1.86 (2H, m), 1.57 (1H, m), 1.33 (3H, t, J=6.0 Hz), 1.30(1H, m).

Workup

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

Sources & evidence

ORD record
ord-230635c52f84493da06ea0cf38537333
Source dataset
uspto-grants-2007_05
Patent number
US07217731B2

Reaction notes

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