Ammonium Chloride → tert-Butyl 3-amino-4-hydroxypyrrolidine-1-carboxylate

Temperature

60 °C

6-Oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (12.1 g, 65.3 mmol) was dissolved in a 8:1 methanol/water mixture (108 mL). Ammonium chloride (15 g) and sodium azide (21.4 g, 329 mmol) was added and the reaction mixturewas heated at 60° C. overnight. After dilution with ether (500 mL), the reaction mixturewas washed with saturated aqueous NaHCO3 (200 mL) and brine (200 mL), dried with MgSO4 and evaporated under vacuum. The crude product was dissolved in methanol (200 mL). 10% Palladium on activated carbon (1.5 g) was added and the reaction mixturewas stirred at ambient temperature under a hydrogen atmosphere until TLC analysis showed the disappearance of the starting material. The reaction mixture was filtered through a pad of Celite and evaporated to dryness under vacuum. The product was purified by flash chromatography on silica gel using 5% methanol in ethyl acetate to 20% methanol, 3% triethylamine in ethyl acetate to give 4.3 g of 3-amino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester as yellowish solid.

1. washAfter dilution with ether (500 mL), the reaction mixturewas washed with saturated aqueous NaHCO3 (200 mL) and brine (200 mL)
2. dry with materialdried with MgSO4
3. customevaporated under vacuum
4. dissolutionThe crude product was dissolved in methanol (200 mL)
5. addition10% Palladium on activated carbon (1.5 g) was added
6. filtrationThe reaction mixture was filtered through a pad of Celite
7. customevaporated to dryness under vacuum
8. customThe product was purified by flash chromatography on silica gel using 5% methanol in ethyl acetate to 20% methanol, 3% triethylamine in ethyl acetate

ORD record

ord-076b5ec597b24e0bbbdaac2bfe700e4d

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662849B2