4-Acetylpyridine → 1-(Pyridin-4-yl)-1-(2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)ethanol

HRID 1777464

Reaction equation

[Li]CCCC.[F:6][C:7]([F:20])([F:19])[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[CH:10][CH:9]=1.[N:21]1[CH:26]=[CH:25][C:24]([C:27](=[O:29])[CH3:28])=[CH:23][CH:22]=1>C1COCC1>[N:21]1[CH:26]=[CH:25][C:24]([C:27]([C:16]2[S:15][C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:7]([F:6])([F:19])[F:20])=[CH:13][CH:12]=3)=[N:18][CH:17]=2)([OH:29])[CH3:28])=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of DIPA (0.09 mL, 0.000655 mmol) in THF (7 mL) at −78° C. was added n-BuLi (0.54 mL, 0.000873 mmol) and the mixture stirred at 0° C. for 30 min. After the reaction mixture was cooled to −78° C., a solution of 2-(4-(trifluoromethyl)phenyl)thiazole (0.1 g, 0.000436 mmol) in THF (2 mL) was added dropwise over 30 min 1-(Pyridin-4-yl)ethanone (0.05 mL, 0.000480 mmol) in THF (2 mL) was then added and the reaction mixture was stirred for an additional 1 hour at −78° C. The work up and purification was done as described in Example 23, Step 2, to provide 1-(pyridin-4-yl)-1-(2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)ethanol (0.12 g, 80%) as off-white solid in 99% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 8.52 (dd, 2H), 8.07 (d, 2H), 7.90 (s, 1H), 7.80 (d, 2H), 7.50 (dd, 2H), 6.71 (s, 1H), 1.94 (s, 3H); LC-MS m/z calculated for [M+H]+ 351.07. found 351.1.

Workup

temperatureAfter the reaction mixture was cooled to −78° C.
additionwas then added
stirringthe reaction mixture was stirred for an additional 1 hour at −78° C
customThe work up and purification

Sources & evidence

ORD record: ord-defe4bc41a1f400bbc114b1133856f56
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266873B2

Linked notes

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