Triethylamine → HCID 24508060, compound

Participants

Reaction Steps

Triethylamine (12.7 mL, 91.1 mmol) was added to a solution of 4-chloro-quinazoline (5.00 g, 30.4 mmol) and ethyl isonipecotate (4.78 g, 30.4 mmol) in THF (80 mL) at ambient temperature. After being refluxed for 12 hours, the mixture was concentrated in vacuo, and the resulting residue was partitioned between DCM and aqueous 0.1 M NaOH. The separated DCM layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting solids were suspended in Et2O and filtered to give 1-quinazolin-4-yl-piperidine-4-carboxylic acid ethyl ester (8.0 g, 28.0 mmol). This material was dissolved in EtOH (50 mL) and THF (50 mL) followed by the addition of NaOH (3.73 g, 93.4 mmol) in H2O (50 mL). After being stirred for 12 hours, the mixture was neutralized with 1.0N HCl (93.5 mL) and concentrated in vacuo. After the volatile organics are removed, a white precipitate forms in the resulting aqueous solution. The solid was filtered off and air-dried to give 1-quinazolin-4-yl-piperidine-4-carboxylic acid (6.5 g). 1H NMR (DMSO-d6, 400 MHz) δ 12.28 (bs, 1H), 8.57 (s, 1H), 7.91 (m, 1H), 7.75 (m, 2H), 7.49 (m, 1H), 4.13 (m, 2H), 3.22 (m, 2H), 2.57 (m, 1H), 1.93 (m, 2H), 1.72 (m, 2H).

Provenance & Evidence