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

온도

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 mixture was heated at 60° C. overnight. After dilution with ether (500 mL), the mixture was 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 mixture was stirred at ambient temperature under a hydrogen atmosphere until TLC analysis showed the disappearance of the starting material. The mixture was filtered through a pad of Celite and evaporated to dryness under vacuum. The product was purified by flash chromatography on silica gel. Eluent: 5% methanol in ethyl acetate to 20% methanol, 3% triethylamine in ethyl acetate. Yield: 4.3 g 3-amino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester as yellowish solid.

1. washAfter dilution with ether (500 mL), the mixture was 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 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

ORD 기록

ord-ebb0b2da0c964d3aa4cc4359b2849b20

출처 데이터셋

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07196099B2