1-Bromo-4-phenylmethoxybenzene → (4-(Benzyloxy)phenyl)(5-bromo-2-methylphenyl)methanol

HRID 1499302Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Br:21][C:22]1[CH:23]=[CH:24][C:25]([CH3:30])=[C:26]([CH:29]=1)[CH:27]=[O:28]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:27]([C:26]2[CH:29]=[C:22]([Br:21])[CH:23]=[CH:24][C:25]=2[CH3:30])[OH:28])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-benzyloxybromobenzene (2.63 g, 10 mmol) in THF (50 mL) at −78° C. under nitrogen was slowly added n-butyllithium (2.5 M in hexanes, 4.4 mL, 11 mmol). The reaction was stirred for 30 minutes. 5-Bromo-2-methylbenzaldehyde (32, 1.99 g, 10 mmol) in THF (4 mL plus 1 mL rinse) was added slowly. The reaction was allowed to slowly warm to about 0° C. over 2 hours, then quenched with saturated aqueous NH4Cl, diluted with ether, washed with H2O and brine, dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel flash chromatography (gradient 0-25% EtOAc/hexanes) to give 3.12 g (82% yield) of the title compound 33 as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.80 (d, J=2.3 Hz, 1 H), 7.36-7.47 (m, 4 H), 7.29-7.36 (m, 2 H), 7.18-7.24 (m, 2 H), 6.99 (d, J=8.1 Hz, 1 H), 6.88-6.97 (m, 2 H), 5.89 (d, J=3.5 Hz, 1 H), 5.06 (s, 2 H), 2.12 (s, 3 H), 2.06 (d, J=3.5 Hz, 1 H); MS (ES+) [M-OH]+=365, 367.

Workup

customat −78° C.
customquenched with saturated aqueous NH4Cl
additiondiluted with ether
washwashed with H2O and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by silica gel flash chromatography (gradient 0-25% EtOAc/hexanes)

Sources & evidence

ORD record: ord-f67349f5542e4cb695827d41a0b0907c
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200025B2

Reaction notes

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