Cyclohexanemethanol → 3-(Cyclohexylmethoxy)-5-(methylsulfanyl)-1,2-thiazole-4-carbonitrile

Participants

Reaction Steps

3-hydroxy-5-methylsulfanyl-isothiazole-4-carbonitrile (10 g, 58 mmol) is dissolved in anhydrous THF (200 mL). Cyclohexylmethanol (11 mL, 87.1 mmol) and diphenyl-2-pyridyl-phosphine (30.5 g, 116 mmol) are added to the solution. Diazenedicarboxylic acid bis(N′-methylpiperazide) (32.7 g, 116 mmol) is slurried in anhydrous THF (200 mL) and added dropwise over 1 hour to the reaction. The reaction is stirred at room temp. for 3 days and then diluted with water and extracted with EtOAc (100 mL×3). The combined organics are then dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography (20% EtOAc/hexane) followed by a second chromatography (10% EtOAc/hexane) provides 3 (7.3 g, 52%). 1H NMR (d6 DMSO): δ 4.18 (2H, d, J=6.3 Hz), 2.76 (3H, s), 1.64–1.81 (6H, m), 1.16–1.27 (3H, m), 1.00–1.13 (2H, m).

Provenance & Evidence