Tert-butyl 4-hydroxypiperidine-1-carboxylate → HCID 44128630, compound

Participants

Reaction Steps

22.6 g Potassium tert. butoxide, 33.2 g 4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester and 300 mL MTB ether were stirred for 1 h at reflux. A solution of 20.3 g 4-Fluoro-2-methyl-benzonitrile, dissolved in 250 mL MTB ether was added within 20 min to the suspension and heating to reflux was continued for 7 h. The reaction was quenched with water. The organic layer was separated and washed with water and concentrated to give 54.8 g (yield 92%) of 4-(4-Cyano-3-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (500 MHz, d6-DMSO) δ 1.40 (s, 9H), 1.47-1.55 (m, 2H), 1.88-1.95 (m, 2H), 2.43 (s, 3H), 3.13-3.22 (m, 2H), 3.63-3.70 (m, 2H), 4.66-4.73 (m, 1H), 6.96 (dd, J=8.6, 2.4 Hz, 1H), 7.07 (d, J=2.3 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H).

Provenance & Evidence