Ethyl chloroformate → Tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate

HRID 2069091Notes

Reaction equation

HRID 2069091 reaction equation
C(Cl)(=O)OCC.[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH:15]1[C:20](O)=[O:21])=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(C(C)C)CC)(C)C.[BH4-].[Na+]>CO.C1COCC1>[OH:21][CH2:20][CH:15]1[CH2:16][O:17][CH2:18][CH2:19][N:14]1[C:12]([O:11][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:13]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 27601334-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 5058359Tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylateYield 74.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl chlorocarbonate (149 μL; TCI) was added to a THF (8 mL) solution of morpholine-3, 4-dicarboxylic acid 4-tert-butyl ester (300 mg; Ast) and diisopropylethylamine (560 μL; WAKO) with ice cooling and the resulting mixture was stirred at room temperature for 1 and half hours. Sodium tetrahydroborate (197 mg; WAKO) was added at room temperature, the resulting mixture was stirred for 15 minutes followed by the addition of methanol (1.2 mL) with ice cooling, and the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture solution was concentrated under reduced pressure, ethyl acetate and saturated aqueous sodium bicarbonate solution were added to extract the reaction mixture, then the organic layer was dried, and the solvent was evaporated under reduced pressure to give the title compound (209 mg).

Workup

  1. stirringthe resulting mixture was stirred for 15 minutes
  2. stirringthe resulting mixture was stirred at room temperature for 2 hours
  3. concentrationThe reaction mixture solution was concentrated under reduced pressure, ethyl acetate and saturated aqueous sodium bicarbonate solution
  4. additionwere added
  5. extractionto extract the reaction mixture
  6. customthe organic layer was dried
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-d33858a942ae4b9bbd474c7030ef636b
Source dataset
uspto-grants-2012_10
Patent number
US08299055B2

Reaction notes

Loading…