[1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic Acid-tert-butyl Ester → (1(S)-Acetyl-2,2-dimethylpropyl)carbamic Acid-tert-butyl Ester

Temperature

-70 °C

[1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic acid-tert-butyl ester (2.0 g, 7.3 mmol) was dissolved in, freshly distilled THF under an argon atmosphere. The solution was cooled to −78° C. whereupon MeLi (15.6 mL, 1.4 M in diethyl ether, 21.9 mmol, 3 eqv) was added dropwise maintaining an internal temperature <−70° C. The reaction was stirred at −70° C. for 30 minutes before warming to −30° C. for a further 30 minutes. After this time TLC analysis indicated the complete consumption of starting material. Saturated aqueous ammonium chloride solution (10 mL) was added and the reaction allowed to warm to room temperature. The aqueous phase was extracted with ethyl acetate (3×30 mL). The organic phases were washed with water (3×50 mL) and brine (50 mL), dried over MgSO4, filtered and the solvents removed in vacuo to give a crude yellow oil. Purification by column chromatography (SiO2, 20% ethyl acetate in hexanes) afforded the title compound as a colourless oil (1.355 g, 84%).

1. additionwas added dropwise
2. temperaturemaintaining an internal temperature <−70° C
3. temperaturebefore warming to −30° C. for a further 30 minutes
4. customthe complete consumption of starting material
5. additionSaturated aqueous ammonium chloride solution (10 mL) was added
6. temperatureto warm to room temperature
7. extractionThe aqueous phase was extracted with ethyl acetate (3×30 mL)
8. washThe organic phases were washed with water (3×50 mL) and brine (50 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. customthe solvents removed in vacuo
12. customto give a crude yellow oil
13. customPurification by column chromatography (SiO2, 20% ethyl acetate in hexanes)

ORD record

ord-35cda8df68be4bb09ed43e1b5cbe1c0e

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06716878B1