Tetrahydrofuran → 2-(4-((2-(Cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)ethanol

HRID 1508906Notes

Reaction equation

[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21](OC)=[O:22])=[CH:16][CH:15]=3)[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C.C1COCC1>ClCCl>[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][OH:22])=[CH:16][CH:15]=3)[CH:10]=[C:9]([C:25]([F:27])([F:28])[F:26])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

A 25-mL round bottom flask was charged with methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate (0.069 g, 0.17 mmol) and dichloromethane (6 mL) at 0° C. A 1M solution of DIBAL-H in THF (0.70 mL, 0.70 mmol) was added and the resulting solution was stirred at 0° C. for 1 h until the starting material was consumed (monitored by LCMS analysis). The reaction was quenched with methanol then absorbed onto silica (2 g) and concentrated under reduced pressure. Purification by column chromatography on silica using hexanes/ethyl acetate (10:0 to 1:1) as the eluent afforded the title compound (0.055 g, 87%) as a white solid. MW=366.38. M.p. 48-50° C. 1H NMR (DMSO-d6, 500 MHz) δ 7.51 (s, 1H), 7.23 (d, J=7.5 Hz, 2H), 7.16 (d, J=8.0 Hz, 2H), 5.38-5.32 (m, 1H), 4.58 (t, J=5.5 Hz, 1H), 4.09 (s, 2H), 3.56 (q, J=6.0 Hz, 2H), 2.68 (t, J=7.0 Hz, 2H), 2.00-1.89 (m, 2H), 1.77-1.66 (m, 4H), 1.66-1.55 (m, 2H); APCI MS m/z 367 [M+H]+.

Workup

customwas consumed (monitored by LCMS analysis)
customThe reaction was quenched with methanol
customthen absorbed onto silica (2 g)
concentrationconcentrated under reduced pressure
customPurification by column chromatography on silica

Sources & evidence

ORD record: ord-2f0a1f23a16046f28a9ad9c1002bfbdf
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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