Methanol → (R)-tert-Butyl 5-hydroxy-7-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate
Reaction equation
CSC.B.B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@H]2N1CCC2.[CH3:26][C:27]1[C:45]([C:46]([F:49])([F:48])[F:47])=[CH:44][C:30]2[N:31]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32][CH2:33][CH2:34][C:35](=[O:36])[C:29]=2[CH:28]=1.CO>ClCCl>[OH:36][C@@H:35]1[CH2:34][CH2:33][CH2:32][N:31]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:30]2[CH:44]=[C:45]([C:46]([F:49])([F:47])[F:48])[C:27]([CH3:26])=[CH:28][C:29]1=2Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
Add a solution of borane dimethylsulfide complex (3.8 mL, 7.58 mmol, 2 M in tetrahydrofuran) dropwise to a solution of (S)-2-methyl-CBS-oxazaborolidine (9.5 mL, 9.48 mmol, 1M in toluene) in dichloromethane (20 mL) at −30° C. under nitrogen. Stir the mixture for 30 min and add a solution of tert-butyl 7-methyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (2.17 g, 6.32 mmol) in dichloromethane (20 mL) dropwise and warm the mixture slowly to 0° C. Pour the mixture into methanol (200 mL) at −20° C. and slowly warm the stirring mixture to room temperature over 1 h. Remove the solvents under reduced pressure and purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (1:2), to provide the title compound as a colorless oil (1.65 g, 76%). APCI MS m/z 345 (M+H)+.
Workup
- temperatureslowly warm the stirring mixture to room temperature over 1 h
- customRemove the solvents under reduced pressure
- custompurify the residue by column chromatography on silica gel
- washeluting with ethyl acetate/hexanes (1:2)
Sources & evidence
- ORD record
- ord-1f4f683537744f0d91bd5e15662751a2
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07786108B2
Reaction notes
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