Sodium Hydroxide → (R)-2-(tert-butoxycarbonyl)amino-2-(4-benzyloxyphenyl)ethanol

To a solution of t-butyl carbamate (3.65 g, 30.5 mmol) in n-propanol (40 ml) was added the solution of sodium hydroxide (1.26 g, 30.5 mmol) in water (75 ml), then added t-butyl hypochloride (3.5 ml, 30.5 mmol), made freshly (Org. Syn. 184) in a light-off hood. The mixture was stirred for 5 minutes at room temperature. This reaction mixture was then placed in an ice-bath, (DHQD)2PHAL (0.492 g, 0.6 mmol) in n-propanol (40 ml) and 1-Benzyloxy-4-vinyl-benzene (2.10 g, 10 mmol) in n-propanol (70 ml) were added sequentially, stirred for 6 minutes. K2OsO2 2H2O (0.147 g, 0.4 mmol) was added directly at 0° C. The final reaction mixture was stirred for 1.5 hrs to generate a light yellow clear solution. A saturated solution of sodium sulfite (100 ml) was added to quench the reaction at 0° C. Excessive n-propanol was removed in a high vacuum. The aqueous phase was extracted by ethyl acetate (3×30 ml). The combined organic layers were washed with brine (2×30 ml), then dried over MgSO4, filtered and concentrated to give a yellow crude solid. The crude product was purified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexanes to afford a white solid (2.01 g, 59% yield, about 13% of regio-isomer): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.39 (m, 5H), 7.23 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.6 Hz, 2H), 5.15 (d, J=5.6 Hz, 1H), 5.07 (s, 2H), 4.74 (d, J=1.0 Hz, 1H), 3.84 (t, J=5.3 Hz, 2H), 2.37 (br. s., 1H), 1.42 (m, 9H); LCMS (ESI) m/e 344.2 [(M+H), calcd for C20H26NO4 344.4].

1. customThis reaction mixture was then placed in an ice-bath
2. stirringstirred for 6 minutes
3. customThe final reaction mixture
4. stirringwas stirred for 1.5 hrs
5. customto quench
6. customthe reaction at 0° C
7. customExcessive n-propanol was removed in a high vacuum
8. extractionThe aqueous phase was extracted by ethyl acetate (3×30 ml)
9. washThe combined organic layers were washed with brine (2×30 ml)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customto give a yellow crude solid
14. customThe crude product was purified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexanes
15. customto afford a white solid (2.01 g, 59% yield, about 13% of regio-isomer)

ORD record

ord-83a45eba8ab94bb78b693937c77be6c9

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497271B2