Methyl chloroformate → N-(Methoxycarbonyl)-L-tert-leucine

Temperature

60 °C

A solution of L-tert-Leucine (25 g, 190.58 mmol) in a mixture of dioxane (100 mL) and aqueous NaOH solution (315 mL, 2N) was treated dropwise with methyl chloroformate (29.3 mL, 379.19 mmol), keeping the internal temperature below 50° C. The mixture was warmed to 60° C. and stirred for 18 hours, cooled to 25° C. and extracted with dichloromethane. The aqueous phase was cooled to 0° C. and the pH was adjusted to about 1-2 with concentrated HCl. The mixture was partitioned between ethyl acetate and water. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. A solution of the concentrate in ether was treated with hexanes to afford the crystalline product (33.22 g, 92% yield), which was collected by filtration.

1. customthe internal temperature below 50° C
2. temperaturecooled to 25° C.
3. extractionextracted with dichloromethane
4. temperatureThe aqueous phase was cooled to 0° C.
5. customThe mixture was partitioned between ethyl acetate and water
6. washThe combined organic extracts were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. concentrationA solution of the concentrate in ether
11. additionwas treated with hexanes

ORD record

ord-79d590afa1cf46d3aa4741c2de94b4cb

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834043B2