1-Bromo-3-chlorobenzene → HCID 66763576, compound

HRID 2167517Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[CH:3]=1.C([Li])(C)(C)C.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:27]=[CH:28][CH:29]=1)[CH2:19][N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1>C(OCC)C>[Cl:8][C:4]1[CH:3]=[C:2]([C:23]2([OH:26])[CH2:22][CH2:21][N:20]([CH2:19][C:18]3[CH:27]=[CH:28][CH:29]=[C:16]([O:15][CH3:14])[CH:17]=3)[CH2:25][CH2:24]2)[CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To 1-bromo-3-chlorobenzene (480 mg, 2.51 mmol) in diethyl ether (10 mL), at −78° C., was added t-butyllithium (3.0 mL of a 1.7 M solution in hexanes, 5.0 mmol) dropwise. After 1 h, a solution of 1-(3-methoxybenzyl)piperidin-4-one (500 mg, 2.28 mmol) in diethyl ether (5 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 0.5 h, warmed to ambient temperature and quenched with saturated ammonium chloride. The organic layer was separated, washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (10% ethyl acetate/methylene chloride to ethyl acetate) gave 4-(3-chlorophenyl)-1-(3-methoxybenzyl)piperidin-4-ol (668 mg, 80%) as an oil: 1H NMR (CDCl3, 300 MHz) δ 7.53-7.52 (m, 1H), 7.40-7.36 (m, 1H), 7.30-7.20 (m, 3H), 6.96-6.93 (m, 2H), 6.82-6.79 (m, 1H), 3.82 (s, 3H), 3.58 (s, 2H), 2.82-2.70 (m, 2H), 2.49-2.41 (m, 2H), 2.18-2.08 (m, 2H), 1.73-1.67 (m, 2H), 1.60 (s, 1H).

Workup

temperaturewarmed to ambient temperature
customquenched with saturated ammonium chloride
customThe organic layer was separated
washwashed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customPurification by silica gel chromatography (10% ethyl acetate/methylene chloride to ethyl acetate)

Sources & evidence

ORD record: ord-4e902465ebd147f48175ce15d82e29f0
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045468B2

Reaction notes

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