Tetrahydrofuran → 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), titanium (IV) ethoxide (100 ml) and 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). The mixture was stirred at 0° C. for 3 hours and then warmed to room temperature. The reaction was quenched with MeOH and stirred for 30 minutes. Then to the mixuture water was added. After stirring for 10 minutes, the resulting suspension was filtered through a celite pad and the filtered cake was washed with EtOAc. The filtrate was concentrated under reduced pressure to give a residue, which was applied to a silica gel chromatography column and eluted with a volume mixture of DCM and EtOAc (1/1) to afford 4.3 g (23% yield) of the title compound as pale yellow solids.

1. temperatureThe mixture was cooled to room temperature
2. stirringThe mixture was stirred at 0° C. for 3 hours
3. temperaturewarmed to room temperature
4. customThe reaction was quenched with MeOH
5. stirringstirred for 30 minutes
6. additionThen to the mixuture water was added
7. stirringAfter stirring for 10 minutes
8. filtrationthe resulting suspension was filtered through a celite pad
9. washthe filtered cake was washed with EtOAc
10. concentrationThe filtrate was concentrated under reduced pressure
11. customto give a residue, which
12. washeluted with a volume mixture of DCM and EtOAc (1/1)

ORD record

ord-4516348dd394486280fad9a47c69c668

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622589B2