Reaction #2122522

Reaction equation

ClCO2Me

(R)-tert-butyl 2-amino-2-phenylacetate HCl

diisopropylethylamine

→

(R)-tert-butyl 2-(methoxycarbonylamino)-2-phenylacetate

Yield 71.6%

Solvents

THF

Conditions

Workup

1. 1
   OtherThe volatile component was removed in vacuo
2. 2
   Otherthe residue was partitioned between water (100 mL) and ethyl acetate (200 mL)
3. 3
   WashThe organic layer was washed with 1N HCl (25 mL) and saturated NaHCO3 solution (30 mL)
4. 4
   Dryingdried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe resultant colorless oil was triturated from hexanes
8. 8
   Filtrationfiltered
9. 9
   Washwashed with hexanes (100 mL)

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. 1): RT=1.53 min; ˜90% homogeneity index; LC/MS: Anal. Calcd. for [M+Na]+ C14H16NNaO4: 288.12; found 288.15.

Source