4-Fluorobenzonitrile → 4-(4-(Hydroxymethyl)piperidin-1-yl)benzonitrile
Reaction equation
Cl.[OH:2][CH2:3][CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.F[C:11]1[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=1.C(N(C(C)C)C(C)C)C>>[C:15]([C:14]1[CH:17]=[CH:18][C:11]([N:7]2[CH2:8][CH2:9][CH:4]([CH2:3][OH:2])[CH2:5][CH2:6]2)=[CH:12][CH:13]=1)#[N:16]Participants
4
Procedure
A solution of 12.2 g of 4-hydroxymethyl-piperidine-hydrochloride, 9.8 g of 4-fluorobenzonitrile and 28.3 ml of N-ethyl-diisopropylamine is heated to 140° C. for 4 hours. After cooling, it is chromatographed over silica gel using methylene chloride and methylene chloride/ethyl acetate (1:1) as eluant. After the solvent has been removed under reduced pressure the residue remaining is triturated with petroleum ether and suction filtered. Yield: 5.1 g (29% of theory), Melting point: 148°-150° C.