Hydrochloric Acid → tert-Butyl (4-hydroxy-2-methylbutan-2-yl)carbamate

Temperature

0 °C

At 0° C., ethyl chloroformate (1.10 ml, 11.5 mmol) was given dropwise to a solution of 3-tert-butoxycarbonylamino-3-methylbutanoic acid (2.50 g, 11.5 mmol) and triethylamine (1.92 ml, 13.8 mmol) in THF (10 ml). The solution was stirred for 40 min at 0° C. The obtained precipitate was filtered off and washed with THF (20 ml). The liquid was immediately cooled to 0° C. A 2M solution of lithium boronhydride in THF (14.4 ml, 28.8 mmol) was added dropwise. The solution was stirred at 0° C. for 2 h, and then warmed to room temp. over a period of 4 h. It was cooled to 0° C. Methanol (5 ml) was added carefully. 1N Hydrochloric acid (100 ml) was added. The solution was extracted with ethyl acetate (2×100 ml, 3×50 ml). The combined organic layers were washed with saturated solution of sodium hydrogencarbonate (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was chromatographed on silica (110 g) with ethyl acetate/heptane 1:2 to give 1.84 g of 3-hydroxy-1,1-dimethylpropylcarbamic acid tert-butyl ester.

1. customAt 0° C.
2. filtrationThe obtained precipitate was filtered off
3. washwashed with THF (20 ml)
4. temperatureThe liquid was immediately cooled to 0° C
5. stirringThe solution was stirred at 0° C. for 2 h
6. temperaturewarmed to room temp. over a period of 4 h
7. temperatureIt was cooled to 0° C
8. extractionThe solution was extracted with ethyl acetate (2×100 ml, 3×50 ml)
9. washThe combined organic layers were washed with saturated solution of sodium hydrogencarbonate (100 ml)
10. dry with materialdried over magnesium sulfate
11. customThe solvent was removed in vacuo
12. customThe crude product was chromatographed on silica (110 g) with ethyl acetate/heptane 1:2

ORD record

ord-dc5cbb4ee4754733b651c72f1a19c8b4

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06013658