1-(3,5-DIFLUOROPHENYL)ETHANOL synthesis

Yield:467223-90-1 90%

Reaction Conditions:

with borane-THF

Steps:

356
The synthesis of 2- (3, 5-Difluorophenyl)-1-oxiranylethanol (67) followed that reported in Kurihara, M. et al. Tetrahedron Left. 1999,40, 3183-3184 for the synthesis of 2-phenyl-1-oxiranylethanol. 2-(3, 5-Difluorophenyl)-1-oxiranylethanol : Rf = 0.42 (30% EtOAc/hexanes); retention time (min) = 1.350 (method [1] ) ; MS (ESI) 242.3 (84), 201.3 (26), 183.3 (100). The synthesis of 2- [2- (3, 5-Difluorophenyl)-1-methoxyethyl] oxirane (68) followed the method of Boeckman, R. K. Jr.; Liu, X. Synthesis 2002,2138-2142. 2- (3, 5-Difluorophenyl)-1-oxiranylethanol (67) (411 mg, 2.05 mmol) was combined with silver (l) oxide (1.934 g, 8.34 mmol) in iodomethane (5.2 mL, 83.3 mmol), and heated to gentle reflux (45 °C bath) for 20 h. The mixture was then diluted with diethyl ether, filtered through diatomaceous earth, and the filtrate concentrated under reduced pressure to give 68. Flash chromatography (10% EtOAc/hexanes elution) afforded 273 mg (63%) of the product as an oil : Rf = 0.26 (10% EtOAc/hexanes); retention time (min) = 1.895 (major), 1.951 (minor), method [1] ; MS (ESI) 256.3 (100), 237.3 (22), 215.3 (26).

References:

ELAN PHARMACEUTICALS, INC. WO2005/87751, 2005, A2 Location in patent:Page/Page column 237

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