4-Bromoanisole → HCID 118207551, compound
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[O:15]=[C:16]1[CH2:22][CH2:21][CH2:20][CH2:19][N:18]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:17]1>C1COCC1>[OH:15][C:16]1([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[CH2:22][CH2:21][CH2:20][CH2:19][N:18]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:17]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of 1-bromo-4-methoxybenzene (0.67 mL, 5.4 mmol) in THF (50 mL) at −78° C. was added n-butyllithium (5 mL, 8 mmol) and the reaction mixture was stirred at −78° C. for 2 h. Then was added tert-butyl 3-oxoazepane-1-carboxylate (1.14 g, 5.4 mmol) at −78° C. and the reaction mixture was warmed to room temperature over 12 h. It was then quenched with saturated NH4Cl at 0° C., and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (24 g) using 10% ethyl acetate in hexane to yield tert-butyl 3-hydroxy-3-(4-methoxyphenyl)azepane-1-carboxylate (1.2 g, 57%) as a colorless gum. LCMS: R.T. 1.03 min. LCMS (ES-API), m/z 204 (M-117).
Workup
- temperaturethe reaction mixture was warmed to room temperature over 12 h
- customIt was then quenched with saturated NH4Cl at 0° C.
- extractionextracted with ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by flash chromatography on silica gel (24 g)
Sources & evidence
- ORD record
- ord-7334087485c941399263d8c09613fba6
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221796B2
Reaction notes
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