1-tert-butyl 2-methyl (2R,4S)-4-fluoropyrrolidine-1,2-dicarboxylate

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

Procedure: Add lithium borohydride (0.43 g, 19.6 mmol) to an ice cold solution of 4-(S)-fluoropyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.9 g, 13.08 mmol) in THF (50 mL). Warm to room temperature over 18 h. Cool in ice bath. Slowly add acetic acid (3 mL) and water and extract with ethyl acetate. Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a thick oil (2.90 g, 100%). Cool in ice bath Slowly add acetic acid (3 mL) and water and extract with ethyl acetate Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)

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

Procedure: Add lithium borohydride (0.43 g, 19.6 mmol) to an ice cold solution of 4-(S)-fluoropyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.9 g, 13.08 mmol) in THF (50 mL). Warm to room temperature over 18 h. Cool in ice bath. Slowly add acetic acid (3 mL) and water and extract with ethyl acetate. Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a thick oil (2.90 g, 100%). Cool in ice bath Slowly add acetic acid (3 mL) and water and extract with ethyl acetate Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)

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

Procedure: Add (diethylamino)sulfur trifluoride (3.9 mL, 29.8 mmol) to a −78° C. cooled solution of 4-(R)-hydroxypyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.81 g, 15.54 mmol) in dichloromethane (50 mL). Stir 2 h, then remove cold bath and stir 40 h at room temperature. Cool in ice bath and add saturated sodium bicarbonate solution. Warm to room temperature, dry (magnesium sulfate), concentrate (350 mbar, 25° C.) and purify (silica gel chromatography, eluting with diethyl ether and dichloromethane) to give the title compound as an oil (4.01 g, 97%). remove cold bath stir 40 h at room temperature Cool in ice bath add saturated sodium bicarbonate solution dry (magnesium sulfate) concentrate (350 mbar, 25° C.) purify (silica gel chromatography, eluting with diethyl ether and dichloromethane)

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

Procedure: Add lithium borohydride (0.43 g, 19.6 mmol) to an ice cold solution of 4-(S)-fluoropyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.9 g, 13.08 mmol) in THF (50 mL). Warm to room temperature over 18 h. Cool in ice bath. Slowly add acetic acid (3 mL) and water and extract with ethyl acetate. Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a thick oil (2.90 g, 100%). Cool in ice bath Slowly add acetic acid (3 mL) and water and extract with ethyl acetate Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride dry (magnesium sulfate) concentrate purify (silica gel chromatography, eluting with hexanes and ethyl acetate)

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

Procedure: Add (diethylamino)sulfur trifluoride (3.9 mL, 29.8 mmol) to a −78° C. cooled solution of 4-(R)-hydroxypyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.81 g, 15.54 mmol) in dichloromethane (50 mL). Stir 2 h, then remove cold bath and stir 40 h at room temperature. Cool in ice bath and add saturated sodium bicarbonate solution. Warm to room temperature, dry (magnesium sulfate), concentrate (350 mbar, 25° C.) and purify (silica gel chromatography, eluting with diethyl ether and dichloromethane) to give the title compound as an oil (4.01 g, 97%). remove cold bath stir 40 h at room temperature Cool in ice bath add saturated sodium bicarbonate solution dry (magnesium sulfate) concentrate (350 mbar, 25° C.) purify (silica gel chromatography, eluting with diethyl ether and dichloromethane)