Trichloroisocyanuric Acid → (2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acid

Temperature

0 °C

Sat'd aq NaHCO3 (15 mL) was added to a solution of (R)-tert-butyl 2-(hydroxymethyl)-morpholine-4-carboxylate (1.09 g, 5.0 mmol) in acetone (50 mL), stirred and maintained at 0° C. Solid NaBr (0.1 g, 1 mmol) and TEMPO (0.015 g, 0.1 mmol) were added. Trichloroisocyanuric acid (2.32 g, 10.0 mmol) was then added slowly within 20 min at 0° C. After addition the mixture was warmed to rt and stirred overnight. 2-Propanol (3 mL) was added, and the resulting solution was stirred at rt for 30 min, filtered through a pad of Celite, concentrated under vacuum, and treated with sat'd aq Na2CO3 (15 mL). The aqueous solution was washed with EtOAc (5 mL), acidified with 6 N HCl, and extracted with EtOAc (5×10 mL). The combined organic layers were dried over Na2SO4 and the solvent was removed to give (R)-4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (1.07 g, 92%) as a white solid. 1H NMR (400 MHz, CDCl3): 4.20 (br, 1H), 4.12 (d, 1H), 4.02 (d, 1H), 3.84 (m, 1H), 3.62 (m, 1H), 3.04 (m, 2H), 1.44 (s, 9H); MS m/z 232 (M+H+).

1. additionAfter addition the mixture
2. temperaturewas warmed to rt
3. stirringstirred overnight
4. stirringthe resulting solution was stirred at rt for 30 min
5. filtrationfiltered through a pad of Celite
6. concentrationconcentrated under vacuum
7. additiontreated with sat'd aq Na2CO3 (15 mL)
8. washThe aqueous solution was washed with EtOAc (5 mL)
9. extractionextracted with EtOAc (5×10 mL)
10. dry with materialThe combined organic layers were dried over Na2SO4
11. customthe solvent was removed

ORD record

ord-8d2817e33f4d4b0eb15e5629e4793c55

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07754737B2