Potassium Carbonate → Tert-butyl (3R,4R)-3-azido-4-hydroxypyrrolidine-1-carboxylate

A 500 mL round-bottomed flask was charged with tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (15.42 g, 83.25 mmol), (1S,2S)-(−)-[1,2-cyclohexanediamino-N,N′-bis(3,5-di-t-butylsalicylidene)]chromium (III) chloride (1.18 g, 1.67 mmol) and azidotrimethylsilane (12.8 mL, 91.58 mmol) and the resulting mixture was stirred at ambient temperature under a nitrogen atmosphere for 48 hours. The dark red-brown mixture was diluted with chloroform (250 mL) and washed sequentially with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was dissolved in methanol (830 mL) and treated with potassium carbonate (11.51 g, 83.25 mmol) and the mixture was stirred at ambient temperature for 5 hours. The methanolic solution was filtered through a pad of Celite washed with methanol and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The layers were separated and the aqueous back extracted with EtOAc. The combined organic extracts were washed with saturated sodium bicarbonate solution, water and brine, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (Biotage 40M; 20% ethyl acetate/hexanes) to give (3R,4R)-tert-butyl 3-azido-4-hydroxypyrrolidine-1-carboxylate (18 g, 95%). Enantiomeric excess was determined by Chiral HPLC (AD-H, Chiralcel, 10% EtOH: 90% hexanes at 0.80 mL/min, 94.5% e.e.

1. washwashed sequentially with water and brine
2. dry with materialdried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. dissolutionThe residue was dissolved in methanol (830 mL)
6. stirringthe mixture was stirred at ambient temperature for 5 hours
7. filtrationThe methanolic solution was filtered through a pad of Celite
8. washwashed with methanol
9. concentrationconcentrated under reduced pressure
10. customThe residue was partitioned between water and ethyl acetate
11. customThe layers were separated
12. extractionthe aqueous back extracted with EtOAc
13. washThe combined organic extracts were washed with saturated sodium bicarbonate solution, water and brine
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated
17. customThe residue was purified by column chromatography (Biotage 40M; 20% ethyl acetate/hexanes)

ORD record

ord-f4300a14b74f40b3b3392934ec74065c

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889704B2