L-Threonine → Ethyl5-((1R)-1-{[(R)-tert-butylsulfinyl]amino}ethyl)-2-[(methylsulfonyl)amino]benzoate

Temperature

80 °C

To a mixture of methyl 5-acetyl-2-[(methylsulfonyl)amino]benzoate (13.2 g, 49 mmol, PCT Int. Appl. WO2005003084) in titanium (IV) ethoxide (100 ml) and tetrahydrofuran (THF) (100 ml) was added (R)-(+)-2-methylpropane-2-sulfinamide (5.9 g, 49 mmol, Advanced Asymmmetry) and the mixture was stirred for 16 hours at 80° C. The mixture was cooled to room temperature and then to 0° C. before it was added dropwise into a 0° C. solution of sodium borohydride (7.4 g, 195 mmol). Thre mixture was stirred at 0° C. for 3 hours and then warmed to room temperature. The reaction was quenched with methanol and stirred for 30 minutes. Water was added to the mixture and it was stirred for 10 minutes. The resulting suspension was filtered through a pad of Celite and the filter cake was washed with ethyl acetate. The filtrate was concentrated under reduced pressure to give the residue, which was applied to a silica gel chromatography column and eluted with a volume mixture of dichloromethane and ethyl acetate (1:1) to furnish 4.3 g (23% yield) of the title compound as a slightly yellow solid.

1. temperatureThe mixture was cooled to room temperature
2. temperaturewarmed to room temperature
3. customThe reaction was quenched with methanol
4. stirringstirred for 30 minutes
5. additionWater was added to the mixture and it
6. stirringwas stirred for 10 minutes
7. filtrationThe resulting suspension was filtered through a pad of Celite
8. washthe filter cake was washed with ethyl acetate
9. concentrationThe filtrate was concentrated under reduced pressure
10. customto give the residue, which
11. washeluted with a volume mixture of dichloromethane and ethyl acetate (1:1)

ORD record

ord-495160335735484182ccb75216961d8a

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07566739B2