Dichloromethane → HCID 131731314, compound
Reaction equation
[F:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C@@H:8]([NH2:10])[CH3:9])=[C:4]([C:13]([F:16])([F:15])[F:14])[CH:3]=1.[Si]([O:24][CH2:25][CH:26]=O)(C(C)(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:42]CCl>>[ClH:42].[F:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C@@H:8]([NH:10][CH2:26][CH2:25][OH:24])[CH3:9])=[C:4]([C:13]([F:14])([F:15])[F:16])[CH:3]=1Participants
Procedure
Synthesis of (2S)—N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-2-(trifluoromethyl)phenoxy]propan-2-amine (C8). To a solution of (2S)-1-[4-fluoro-2-(trifluoromethyl)phenoxy]propan-2-amine (C7) (785 mg, 3.31 mmol) in dichloromethane (15 mL) was added {[tert-butyl(dimethyl)silyl]oxy}acetaldehyde (577 mg, 3.31 mmol). After 2 hours, sodium triacetoxyborohydride was added portion-wise. The reaction mixture was allowed to stir at room temperature overnight, then taken up in dichloromethane and washed with saturated aqueous sodium bicarbonate solution and water. The organic layer was concentrated in vacuo, then purified via silica gel chromatography (Gradient: 0 to 7% methanol in ethyl acetate) to afford the title compound as a clear liquid. Yield: 466 mg, 1.18 mmol, 36%. LCMS m/z 396.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 0.07 (s, 6H), 0.90 (s, 9H), 1.19 (d, J=6.4 Hz, 3H), 2.73-2.86 (m, 2H), 3.11-3.19 (m, 1H), 3.74 (dd, J=5.6, 5.4 Hz, 2H), 3.92 (d, J=5.5 Hz, 2H), 6.94 (dd, J=9.0, 4.0 Hz, 1H), 7.15-7.21 (m, 1H), 7.29 (dd, J=8.4, 3.1 Hz, 1H).
Workup
- washwashed with saturated aqueous sodium bicarbonate solution and water
- concentrationThe organic layer was concentrated in vacuo
- custompurified via silica gel chromatography (Gradient: 0 to 7% methanol in ethyl acetate)
Sources & evidence
- ORD record
- ord-c00d3a943e744f40a41ac106ddd74582
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697673B2
Reaction notes
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