Hydroxylamine → HCID 11705851, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension 1-(methylsulfonyl)-4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazine (23 g, 67.8 mmol, prepared as above) in THF (450 mL) at −65° C., was added drop wise a solution of LiHMDS in THF (149 mL, 1.0M solution, 149 mmol). Stirred for 30 minutes. Added diethyl chlorophosphate (11.3 mL, 78 mmol) and stirred for 1 hour. The solution was treated drop wise with a solution of 3-(2-pyridinyl)propaldehyde (12 g, 88.1 mmol) in THF (290 mL) and then allowed to warm to 0° C. over 3 hours before being quenched with a solution of hydroxylamine (41 mL, 50% aqueous solution in water, 680 mmol). The reaction was stirred for 16 hours at RT. The reaction washed with sat. NH4Cl (250 mL) back-extracting with ethyl acetate (250 mL). The combined organic extracts were then dried (brine and MgSO4), filtered and concentrated in vacuo. The residue was then triturated with ether for 1 hour, filtered and dried to give 2-[3-(hydroxyamino)-4-({4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazin-1-yl}sulfonyl)butyl]pyrimidine (31.5 g, 64.3 mmol, 95%).

Provenance & Evidence