Formic Acid → (1-Methylpiperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate

Temperature

95 °C

(1-piperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate (4.07 g, 12.0 mmol) was dissolved in formic acid (20 mL) and 35% aqueous formaldehyde solution (20 mL). The reaction mixture was heated at 95° C. for 90 minutes, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto 1M aq Na2CO3 solution (200 mL), basified to pH10 with 1M aq KOH solution (30 mL) and extracted with DCM (3×100 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 97:2:1 mixture of DCM:MeOH:DIPEA) followed by reverse phase column chromatography (gradient eluting with MeOH in water, 0-80%) to give (1-methylpiperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate (1.30 g, 30.7%) as a white solid.

1. temperaturecooled to room temperature
2. customThe reaction mixture was quenched
3. additionby slowly pouring it onto 1M aq Na2CO3 solution (200 mL)
4. extractionextracted with DCM (3×100 mL)
5. washThe combined organic layers were washed with brine (50 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe residue was purified by normal phase column chromatography (
9. washeluting with DCM
10. additionfollowed by a 97:2:1 mixture of DCM
11. washMeOH:DIPEA) followed by reverse phase column chromatography (gradient eluting with MeOH in water, 0-80%)

ORD record

ord-ef0d73b334794f89a300092708a7999d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093248B2