tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 6-oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (1.50 g, 8.10 mmol) in methylamine (15 mL, 40% solution in water). Warm to 50° C. and stir in a sealed vessel overnight. Dilute the mixture with saturated sodium bicarbonate and extract with dichloromethane (3×). Dry the organics over sodium sulfate, filter, and evaporate. Purify by silica gel chromatography, eluting with 0-10% methanol (2N NH3)/CH2Cl2 to give 1.87 g (97%) of 3-hydroxy-4-methylamino-pyrrolidine-1-carboxylic acid tert-butyl ester as a yellow oil. extract with dichloromethane (3×) Dry the organics over sodium sulfate filter evaporate Purify by silica gel chromatography eluting with 0-10% methanol (2N NH3)/CH2Cl2

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.7 g (0.02 mole) of 1-t-butoxycarbonyl-3,4-epoxypyrrolidine (prepared as described in Preparation 8) were dissolved in 15 ml of ethanol. 7.88 g (0.04 mole) of dibenzylamine were added to the solution, and the mixture was heated under reflux for 10 hours. At the end of this time, the solvent was removed by evaporation under reduced pressure, and the residue was subjected to column chromatography through silica gel, eluted with a 12:88 by volume mixture of ethyl acetate and toluene, to give 1.21 g of 1-t-butoxycarbonyl-3-dibenzylamino-4-hydroxypyrrolidine as a pale yellow oil. the mixture was heated under reflux for 10 hours At the end of this time, the solvent was removed by evaporation under reduced pressure eluted with a 12:88 by volume mixture of ethyl acetate and toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.96 g (0.012 mole) of 70% aqueous m-chloroperbenzoic acid were added to a solution of 1.69 g (0.01 mole) of 1-t-butoxycarbonyl-3-pyrroline [prepared as described in Step (a) above] in 10 ml of chloroform, whilst ice-cooling, and the mixture was stirred with ice-cooling for 8 hours and then with water-cooling for 15 hours. At the end of this time, the reaction mixture was extracted with toluene and the extract was washed, in turn, with an aqueous solution of sodium bicarbonate, a 0.1N aqueous solution of sodium thiosulfate and water. It was then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The residue was subjected to silica gel column chromatography eluted with a 1:5 by volume mixture of ethyl acetate and toluene, to afford 1.09 g of 1-t-butoxycarbonyl-3,4-epoxypyrrolidine as a colorless oily substance. cooling cooling for 8 hours At the end of this time, the reaction mixture was extracted with toluene the extract was washed, in turn, with an aqueous solution of sodium bicarbonate It was then dried over anhydrous sodium sulfate the solvent was removed by evaporation under reduced pressure eluted with a 1:5 by volume mixture of ethyl acetate and toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. washed sequentially with water and brine dried (MgSO4) filtered concentrated under reduced pressure The residue was dissolved in methanol (830 mL) the mixture was stirred at ambient temperature for 5 hours The methanolic solution was filtered through a pad of Celite washed with methanol concentrated under reduced pressure The residue was partitioned between water and ethyl acetate The layers were separated the aqueous back extracted with EtOAc The combined organic extracts were washed with saturated sodium bicarbonate solution, water and brine dried (MgSO4) filtered concentrated The residue was purified by column chromatography (Biotage 40M; 20% ethyl acetate/hexanes)

Conditions: temp:0.00; pressure:0.00; stir: