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

HRID 1844770Notes

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-e5ac89074ed44cdc8b711a6c97e71aed
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946477B2

Reaction notes

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