Cyclopropanecarboxaldehyde → [7-N-(tert-Butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazin-8-yl](cyclopropyl)methanol

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Reaction Conditions

Reaction Steps

To a solution of 1.86 g (6.38 mmol) of 7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (Ex. 2, Step A) in 20 mL of toluene at −78° C. was added 5.88 mL (7.65 mmol, 1.3 M solution in cyclohexane) of sec-butyllithium. The reaction mixture was stirred at −78° C. for 20 min, then 0.524 mL (7.01 mmol) of cyclopropanecarboxaldehyde was added dropwise. The reaction mixture was stirred at −78° C. for 10 min. The −78° C. bath was removed and the mixture was allowed to stir at ambient temperature for 1 h. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted with three portions of ethyl acetate. The combined organic phases were washed with brine, dried over magnesium sulfate, and concentrated to give 2.24 g of crude material. Purification by flash chromatography (silica gel, 7 to 10% ethyl acetate/hexane) gave the title compound as a mixture of 4 diastereomers. LC/MS 363 (M+1).

Provenance & Evidence