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

HRID 2266271Notes

Reaction equation

HRID 2266271 reaction equation
C([O-])(O)=[O:2].[Na+].[OH:6][CH2:7][C@@H:8]1[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]1.[Na+].[Br-].ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O>CC(C)=O.CC1(C)N([O])C(C)(C)CCC1.CC(O)C>[C:17]([O:16][C:14]([N:10]1[CH2:11][CH2:12][O:13][C@@H:8]([C:7]([OH:2])=[O:6])[CH2:9]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 6909Trichloroisocyanuric AcidHCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 1512576(R)-N-Boc-2-hydroxymethylmorpholine

Product 1

HCID 6559076(2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acidYield 92%

Reagents, catalysts & solvents 3

HCID 2724126TempoCatalystHCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

Satd 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 satd 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). These EtOAc extracts were combined, dried over Na2SO4 and concentrated 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, 1 H), 4.12 (d, 1 H), 4.02 (d, 1 H), 3.84 (m, 1 H), 3.62 (m, 1 H), 3.04 (m, 2 H), 1.44 (s, 9 H); MS m/z 232 (M+H+).

Workup

  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 satd aq Na2CO3 (15 mL)
  8. washThe aqueous solution was washed with EtOAc (5 mL)
  9. extractionextracted with EtOAc (5×10 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-eb442ba663d14eda97ffbdf342389e19
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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