(alphaR)-alpha-Methyl-3,5-bis(trifluoromethyl)benzenemethanol → (2R,3R,4S)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(3-bromo-4-fluorophenyl)-4-vinyltetrahydropyran

HRID 747001Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH:14]([CH:15]=[CH2:16])[CH2:13][CH2:12][O:11][CH:10]2[OH:17])[CH:5]=[CH:6][C:7]=1[F:8].[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([C@H:30](O)[CH3:31])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1>ClCCl>[F:18][C:19]([F:33])([F:34])[C:20]1[CH:21]=[C:22]([C@H:30]([O:17][C@@H:10]2[C@@H:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Br:1])[CH:3]=3)[C@H:14]([CH:15]=[CH2:16])[CH2:13][CH2:12][O:11]2)[CH3:31])[CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1

Participants

Conditions

Temperature: 40 °C

Procedure

(±) 3-(3-Bromo-4-fluorophenyl)-4-vinyltetrahydropyran-2-ol (from step f) above; 10.32 g, 0.034 mol), (1R)-3,5-bis(trifluoromethyl)phenylethanol (11 g, 0.042 mol), Amberlyst™ (5 g) and molecular sieves (8 g) were suspended in dichloromethane (20 mL) and the mixture was shaken at 40° C. for 3 days. The resulting yellow solution was filtered, concentrated in vacuo and was purified by chromatography on silica using 1-5% ethyl acetate in hexane as eluant to give a mixture of isomers 1-3 (which were retained) and the desired isomer 4 (3.6 g, 20%) as a colourless oil.

Workup

filtrationThe resulting yellow solution was filtered
concentrationconcentrated in vacuo
customwas purified by chromatography on silica using 1-5% ethyl acetate in hexane as eluant
customto give
additiona mixture of isomers 1-3 (which were retained)

Sources & evidence

ORD record: ord-b1e08f1307834954ab79cf5f562bcb9d
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07393858B2

Reaction notes

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