4-Methylmorpholine → HCID 131720975, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of acid (1) (859 mg, 2.25 mmol) in dichloromethane (8 mL) was added N-methylmorpholine (495 μL, 4.50 mmol). The mixture was cooled to -15° C. (CO2 /benzyl alcohol) and isobutylchloroformate (292 μL, 2.25 mmol) was added. The mixture was stirred at -15° C for 15 minutes followed by the addition of N,O-dimethylhydroxylamine hydrochloride (219 mg, 2.25 mmol). The reaction mixture was stirred at -15° C. for 1 hour, then warmed to room temperature and stirred for a further 15 hours. The mixture was filtered and the filtrate washed sequentially with sodium hydrogen carbonate, water, 10% citric acid and brine, dried (MgSO4) and evaporated to dryness. The crude material was purified by column chromatography to give hydroxamate (2) (694 mg, 730%) as a white foam; m.p. 72°-80° C. (Found: C, 67.4; H, 7.35; N, 9.8%. C24H31N3O4 requires C, 67.7; H, 7.3; N, 9.9%); [α]20 =-9.4° (C=0.3, CHCl3); (S-ISOMER) [α]20 =+8.9° (C=0.3, CHCl3)); υmax (film); 1 695 (CO urethane), 1 657 (CO amide) 741 cm-1 (disubstituted Ph); H (CHCl3), δ6 1.30-2.01 (14H, m, adamantyl), 2.99-3.24 (5H, m, indole CH2 +NCH3), 3.58 (3H, s, OCH3), 4.7 (1H, s, adamantyl 2-H), 5.00 (1H, br d, CH (NHR)CON-), 5.36 (1H br d, urethane NH), 6.92-7.17 (3H, m, indole 2,5,6-H), 7.27 (1H, d, J 8 Hz, indole 7-H), 7.53 (1H, d, J 8 Hz, indole 4-H), 7.99 (1H, s, indole NH).

Provenance & Evidence