Sodium borohydride → 4-[4-[4-(2-Fluoroethyl)-1-piperazinyl]-1-piperidinyl]-2-(methyloxy)aniline

A solution of 1-(2-fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (15.94 g, 43.50 mmol) in THF (200 mL) and MeOH (300 mL) was cooled to 0° C. Nickel(II) chloride hexahydrate (5.18 g, 21.80 mmol) was added in one portion. The solution was stirred for 30 min followed by portion-wise addition of NaBH4 (3.29 g, 87.00 mmol). Prior to warming the reaction to rt additional nickel(II) chloride hexahydrate (5.18 g, 21.80 mmol) and NaBH4 (3.29 g, 87.00 mmol) was added to the reaction. The solvent was removed in vacuo and the residue was taken up in DCM, filtered through Celite®, and washed with EtOAc. Purification by flash chromatography provided the title compound of step E (13.46 g, 40.10 mmol, 92%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (qd, J=11.9, 3.6 Hz, 2H), 1.76 (d, J=12.1 Hz, 2H), 2.12-2.20 (m, 1H), 2.35-2.45 (m, 10H), 2.53 (dt, JHF=28.6 Hz, J=4.9 Hz, 2H), 3.37 (d, J=12.1 Hz, 2H), 3.68 (s, 3H), 4.14 (br. s., 2H), 4.47 (dt, JHF=47.9 Hz, J=4.94 Hz, 2H), 6.24 (dd, J=8.2, 2.4 Hz, 1H), 6.43 (d, J=2.4 Hz, 1H), 6.45 (d, J=8.4 Hz, 1H).

1. temperaturePrior to warming
2. additionwas added to the reaction
3. customThe solvent was removed in vacuo
4. filtrationfiltered through Celite®
5. washwashed with EtOAc
6. customPurification by flash chromatography

ORD record

ord-f22ec1773dc142c0a00cb789f91904fd

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093239B2