Hydroxylamine → HCID 11705851, compound

Temperature

0 °C

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%).

1. stirringThe reaction was stirred for 16 hours at RT
2. washThe reaction washed with sat. NH4Cl (250 mL)
3. extractionback-extracting with ethyl acetate (250 mL)
4. dry with materialThe combined organic extracts were then dried (brine and MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was then triturated with ether for 1 hour
8. filtrationfiltered
9. customdried

ORD record

ord-dccfc69233404a4db435fef5cd57141b

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485644B2