Methanol → HCID 59432328, compound

HRID 507054Notes

Reaction equation

HRID 507054 reaction equation
CSC.B.B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@H]2N1CCC2.[CH2:26]([C:28]1[C:46]([C:47]([F:50])([F:49])[F:48])=[CH:45][C:31]2[N:32]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:33][CH2:34][CH2:35][C:36](=[O:37])[C:30]=2[CH:29]=1)[CH3:27].CO>ClCCl>[C:41]([O:40][C:38]([N:32]1[CH2:33][CH2:34][CH2:35][C@@H:36]([OH:37])[C:30]2[CH:29]=[C:28]([CH2:26][CH3:27])[C:46]([C:47]([F:50])([F:48])[F:49])=[CH:45][C:31]1=2)=[O:39])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 887MethanolHCID 2734713(3aS)-1-methyl-3,3-diphenyl-hexahydropyrrolo(1,2-c)(1,3,2)oxazaboroleHCID 12423031(Dimethyl sulfide)trihydroboronHCID 59432407HCID 59432407, compound

Product 1

HCID 59432328HCID 59432328, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Add a solution of borane dimethylsulfide complex (16.0 mL, 16.0 mmol, 1M in tetrahydrofuran) dropwise to a solution of (S)-2-methyl-CBS-oxazaborolidine (7.50 mL, 7.50 mmol, 1M in toluene) in dichloromethane (100 mL) at −30° C. under nitrogen. Stir the mixture for 30 min and add a solution of tert-butyl 7-ethyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (8.60 g, 24.0 mmol) in dichloromethane (50 mL) dropwise and warm the mixture slowly to 0° C. over a period of 6 h. 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 (0 to 15%), to provide the title compound as a colorless oil (7.62 g, 88%): TLC Rf 0.49 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.21-2.30 (m, 19H), 2.83-2.89 (m, 2H), 4.78-4.80 (m, 1H), 7.31-7.45 (m, 2H); Chiral HPLC (OD Column) 91.6% ee; APCI MS m/z 360 (M+H)+.

Workup

  1. temperatureslowly warm the stirring mixture to room temperature over 1 h
  2. customRemove the solvents under reduced pressure
  3. custompurify the residue by column chromatography on silica gel
  4. washeluting with ethyl acetate/hexanes (0 to 15%)

Sources & evidence

ORD record
ord-6cd611c867f74409a1621cec8d6998f0
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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