4-Methylmorpholine → Morpholine-4-carboxamide

Participants

Reaction Steps

A solution of 100 mg (0.296 mmol) of carboxylic acid derived from D-phenylalanine in 10 mL of THF at -8° C. was treated with 39.0 mg (0.385 mmol) of N-methylmorpholine followed by 54.7 mg (0.400 mmol) of isobutylchloroformate. After stirring for 5 min 34.8 mg (0.400 mmol) of morpholine was added and the reaction mixture allowed to warm to room temperature. After 15 min at room temperature, 50 mL of Et2O was added and the mixture dried over MgSO4, filtered, and concentrated under reduced pressure to afford a residue which was chromatographed (silica, gradient elution 30→100%: EtOAc/hexanes) to provide 112.8 mg (94% yield) of the morpholino amide derived from D-phenylalanine: [α]D24 -95° (c 0.85, CHCl3); IR (CHCl3) 3495 (w), 3000 (s), 2980 (w), 1745 (m), 1700 (s), 1635 (m), 1495 (s), 1445 (m), 1230 (m), 1165 (m), 1115 (m), 1075 (w), 1045 (m), 1025 (w) cm-1 ; 1H NMR (500 MHz, CDCl3) d 7.27-7.22 (m, 3 H), 7.04-7.02 (m, 2 H), 5.71 (s, 1 H), 3.91 (d, J=15.3 Hz, 1 H), 3.75 (s, 3 H), 3.69-3.57 (m, H), 3.50-3.46 (m, 2 H), 3.01 (d, J=13.3 Hz, 1 H), 2.91 (d, J=15.5 Hz, 1 H), 1.46 (s, 9 H); NMR (62.5 MHz, CDCl3) d 172.37, 168.08, 154.19, 135.20, 129.57 (2C), 127.97 (2C), 126.88, 79.18, 66.68, 66.54, 62.44, 52.41, 46.11, 41.81, 40.92, 38.12, 28.20 (3C); high resolution mass spectrum (CI, methane) m/z 407.2123 [(M+H)+ ; calculated for C21H31N2O6 : 407.2182].

Provenance & Evidence