Morpholine → 4-Morpholineacetic acid, 1,1-dimethylethyl ester

HRID 1385883Notes

Reaction equation

HRID 1385883 reaction equation
Br[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1>C1COCC1>[N:10]1([CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 79177tert-Butyl bromoacetate

Product 1

HCID 104428104-Morpholineacetic acid, 1,1-dimethylethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl bromoacetate (1.61 mL, 10.0 mmol) in THF (25 mL) was added morpholine (1.74 mL, 20.0 mmol); the resultant suspension was stirred for 1.5 h and then concentrated. The residue was dissolved in CH2Cl2 (50 mL)/saturated Na2CO3 (75 mL), the layers were separated, and the aqueous layer was extracted with additional CH2Cl2 (2×25 mL). The combined organics were washed with saturated Na2CO3 (20 mL) and brine (30 mL), dried and concentrated to give crude title compound. Tituration with EtOAc (15 mL), filtration, and concentration of the filtrate gave the title compound (2.01 g, 100%) as a colorless oil. TLC: Rf 0.45 (EtOAc). 1H NMR: δ3.79-3.73 (m, 4H, CH2OCH2), 3.11 (s, 2H, CH2), 2.61-2.55 (m, 4H, CH2NCH2), 1.46 (s, 9H, t-Bu). MS (DCI/CH4): m/z (rel intensity) 202 (MH+, 15), 201 (8), 200 (13), 174 (20), 146 (100), 100 (23). HRMS (C10H19NO3) (MH+): calcd, 201.1365; obsd, 201.1371.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)/saturated Na2CO3 (75 mL)
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted with additional CH2Cl2 (2×25 mL)
  5. washThe combined organics were washed with saturated Na2CO3 (20 mL) and brine (30 mL)
  6. customdried
  7. concentrationconcentrated
  8. customto give crude title compound
  9. filtrationTituration with EtOAc (15 mL), filtration, and concentration of the filtrate

Sources & evidence

ORD record
ord-253e80ac1c5d4c4898b3b4afeebe2db4
Source dataset
uspto-grants-2001_07
Patent number
US06265381B1

Reaction notes

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