Diazald → (S)-tert-Butyl 2-(2-diazoacetyl)pyrrolidine-1-carboxylate

Temperature

-20 °C

The solutions of 0.4 g (7 mmol) KOH in 10 ml anhydrous ethanol and 2.14 g (10 mmol) N-methyl-N-nitroso-4-toluenesulfonamide in 30 ml diethyl ether were mixed in the reactor tube of the diazomethane distillation apparatus at 0° C. The reactor tube was kept 5 min at 0° C., and then it was placed into a 60° C. oil bath. The distillation was stopped when about 25 ml of diethyl ether containing the diazomethane was distilled over. The reaction was carried out three times for the next step. 3.14 ml (33 mmol) ethyl chloroformate was added to a solution of 6.46 g (30 mmol) BOC-L-proline and 4.60 ml (33 mmol) triethyl amine in 100 ml tetrahydrofuran at −20° C. The reaction mixture was stirred at −20° C. for 30 min. Then 75 ml diazomethane in ether (containing maximum 0.30 mmol diazomethane) was added to the reaction mixture at −20° C. The reaction mixture was stirred for 1 h at −20° C., and the flask was kept without stirring at −20° C. overnight. 120 ml toluene was added, and the organic phase was washed with saturated NaHCO3 aq and water. The organic phase was dried with anhydrous Na2SO4 and evaporated. Yield of crude product 8.3 g.

1. customwas placed into a 60° C.
2. distillationThe distillation
3. distillationwas distilled over
4. stirringThe reaction mixture was stirred for 1 h at −20° C.
5. stirringwithout stirring at −20° C. overnight
6. washthe organic phase was washed with saturated NaHCO3 aq and water
7. dry with materialThe organic phase was dried with anhydrous Na2SO4
8. customevaporated

ORD record

ord-11eb16ea5f424ce9a074cda662eba0bc

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07173024B2