Sodium borohydride → 1-(2-{[4-bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-yl]oxy}pyridin-3-yl)ethanol
Reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][C:17]1[C:22]([C:23](=[O:25])[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=1.[BH4-].[Na+]>CO>[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][C:17]1[C:22]([CH:23]([OH:25])[CH3:24])=[CH:21][CH:20]=[CH:19][N:18]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 1-(2-{[4-bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-yl]oxy}pyridin-3-yl)ethanone (2) (790 mg, 1.959 mmol, 1.0 equiv.) in MeOH (19.6 mL) was slowly added NaBH4 (148 mg, 3.92 mmol, 2.0 equiv.). The mixture was stirred at room temperature until LCMS showed only the desired product. The solvent was evaporated in vacuo and the mixture was partitioned between EtOAc and saturated aqueous NaHCO3. The combined organic extracts were dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified silica gel chromatography (EtOAc/Hexane gradient from 0 to 100%) to obtain product 3 1H NMR (CDCl3) δ 7.96 (1H, d, J=4.9 Hz), 7.89 (1H, d, J=7.4 Hz), 7.48 (1H, d, J=8.8 Hz), 7.38-7.33 (1H, m), 7.05 (1H, dd, J=7.3, 5.0 Hz), 5.40-5.33 (1H, m), 4.41 (2H, s), 1.70 (3H, d, J=6.48 Hz), 1.08 (9H, s) ppm. LRMS m/z (M+H) 405.0 and 407.0 (intensity ratio ˜1:1) found, 405.1 and 407.1 required. The racemic mixture was further separated via chiral HPLC (ChiralPak IC, EtOH/Heptane with 0.1% DEA=1:9, v/v) to obtain enantiomers 3a and 3b.
Sources & evidence
- ORD record
- ord-7fe03bad9a064651bdc17d44e8ae4f98
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08975286B2
Reaction notes
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