4-Methylmorpholine → HCID 10113858, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (3R)-6-cyclohexyl-3-(3-{[4-(dimethylamino)-1-piperidinyl]carbonyl}-1,2,4-oxadiazol-5yl) hexanoic acid trifluoroacetate (Preparation 26) (702 mg, 1.31 mmol) and N-methylmorpholine (159 μl, 1.45 mmol) in N,N-dimethylformamide (15 ml) was cooled to 0° C. and then treated with dropwise with isobutyl chloroformate (188 μl, 1.45 mmol). The resulting solution was stirred at 0° C. under a nitrogen atmosphere for 45 minutes. Hydroxylamine hydrochloride (274 mg, 3.94 mmol) was then added followed by further N-methylmorpholine (433 μl, 3.94 mmol) and the mixture was stirred for 18 hours being allowed to warm to room temperature over this time. The solvent was removed under reduced pressure and the residue was dissolved in a saturated aqueous solution of sodium carbonate. The pH of the solution was adjusted to 9 by dropwise addition of acetic acid and the product was then extracted with ethyl acetate (×2). The combined organic phases were washed with brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol:0.88 ammonia (90:10:1) then dichloromethane:methanol:0.88 ammonia (80:20:2) to afford the title compound as an oil (23 mg)

Provenance & Evidence