Dimethyl Sulfate → tert-Butyl [(2R)-1-(benzylamino)-3-methoxy-1-oxopropan-2-yl]carbamate

HRID 2093019Notes

Reaction equation

[CH2:1]([NH:8][C:9](=[O:21])[C@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[CH3:24]OS(OC)(=O)=O>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH2:1]([NH:8][C:9](=[O:21])[C@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:18])([CH3:17])[CH3:19])[CH2:11][O:12][CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 10 °C

Procedure

To a stirred solution of 3.2 g (0.01 mol) of Intermediate 4 in 50 mL of toluene was added 0.61 g of tetrabutylammonium bromide and 5 ml of water. The resulting mixture was cooled to 10° C. and a solution of 2.4 g of sodium hydroxide in 2.5 ml of water was added dropwise maintaining the temperature below 10° C. Then, 5.54 g of dimethylsulfate was added dropwise maintaining the temperature below 10° C. After stirring at 10° C. for 2 hours, water (80 mL) was added and the reaction stirred at room temperature overnight. The layers were separated and the aqueous layer was washed twice with dichloromethane (50 mL). The combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine. The solvent was removed under vacuum yielding 3.36 g of a pale red-oil. The oil was not purified and used directly in the following step.

Workup

temperaturemaintaining the temperature below 10° C
temperaturemaintaining the temperature below 10° C
stirringthe reaction stirred at room temperature overnight
customThe layers were separated
washthe aqueous layer was washed twice with dichloromethane (50 mL)
washThe combined organic phase was washed with sodium bicarbonate solution (2×30 mL) and brine
customThe solvent was removed under vacuum

Sources & evidence

ORD record: ord-ab83edf02a53442f96d8bbfcd95bcdf5
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440861B2

Reaction notes

Loading…