Lithiumtriethylborohydride → [4-Bromo-4'-(trifluoromethoxy)biphenyl-3-yl]methanol

HRID 1880567Notes

Reaction equation

C([BH-](CC)CC)C.[Li+].[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=2)=[CH:12][C:11]=1[C:27](OC)=[O:28]>C1COCC1>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[CH:18][C:19]([O:22][C:23]([F:25])([F:26])[F:24])=[CH:20][CH:21]=2)=[CH:12][C:11]=1[CH2:27][OH:28]

Participants

Conditions

Temperature: -10 °C

Procedure

A solution of lithium triethylborohydride (1.0M THF, 10.6 mL) was added dropwise to a THF solution (12 mL) of the intermediate from Step B (2.0 g, 5.33 mmol) cooled in an acetone/ice bath (−10° C.). The solution was stirred at −10° C. until no starting material remained by HPLC (approximately 3 hours). The reaction was quenched with methanol (ca. 10 mL) and concentrated. The residue was partitioned between water and ethyl acetate. The organic phase was washed with water (2×), brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compound. 1H NMR (500 MHz, CDCl3): δ 7.71 (d, J=2.0 Hz, 1H); 7.64-7.60 (m, 3H); 7.37 (dd, J=2.3, 8.2 Hz, 1H); 7.28-7.33 (m, 2H); 4.84 (s, 2H); 2.09 (s, 1H). LCMS1 3.77 min. (M−H2O)=329

Workup

customremained by HPLC (approximately 3 hours)
customThe reaction was quenched with methanol (ca. 10 mL)
concentrationconcentrated
customThe residue was partitioned between water and ethyl acetate
washThe organic phase was washed with water (2×), brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-02622475caed472fa00ff43a173e1b49
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318760B2

Reaction notes

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