Methyl chloroformate → (R)-tert-butyl 2-(methoxycarbonylamino)-2-phenylacetate

HRID 645395Notes

Reaction equation

HRID 645395 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[NH2:6][C@H:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Cl.C(N(C(C)C)CC)(C)C>C1COCC1>[CH3:5][O:4][C:2]([NH:6][C@H:7]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[O:3]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 56777188H-D-Phg-otbu hcl

Product 1

HCID 66648596(R)-tert-butyl 2-(methoxycarbonylamino)-2-phenylacetateYield 71.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

ClCO2Me (3.2 mL, 41.4 mmol) was added dropwise to a cooled (ice/water) THF (410 mL) semi-solution of (R)-tert-butyl 2-amino-2-phenylacetate/HCl (9.877 g, 40.52 mmol) and diisopropylethylamine (14.2 mL, 81.52 mmol) over 6 min, and stirred at similar temperature for 5.5 hours. The volatile component was removed in vacuo, and the residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was washed with 1N HCl (25 mL) and saturated NaHCO3 solution (30 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resultant colorless oil was triturated from hexanes, filtered and washed with hexanes (100 mL) to provide (R)-tert-butyl 2-(methoxycarbonylamino)-2-phenylacetate as a white solid (7.7 g). 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): 7.98 (d, J=8.0, 1H), 7.37-7.29 (m, 5H), 5.09 (d, J=8, 1H), 3.56 (s, 3H), 1.33 (s, 9H). LC (Cond. I): RT=1.53 min; ˜90% homogeneity index; LC/MS: Anal. Calcd. for [M+Na]+ C14H19NNaO4: 288.12; found 288.15.

Workup

  1. customThe volatile component was removed in vacuo
  2. customthe residue was partitioned between water (100 mL) and ethyl acetate (200 mL)
  3. washThe organic layer was washed with 1N HCl (25 mL) and saturated NaHCO3 solution (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resultant colorless oil was triturated from hexanes
  8. filtrationfiltered
  9. washwashed with hexanes (100 mL)

Sources & evidence

ORD record
ord-a5b357bcecdb462cb3df6a95b82ff2e7
Source dataset
uspto-grants-2010_04
Patent number
US07704992B2

Reaction notes

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