ethyl (1R,2R)-2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclopropane-1-carboxylate

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

Procedure: According to the synthesis of Trans-2-(tert-Butoxycarbonylamino-methyl)-cyclopropanecarboxylic acid ethyl ester (intermediate L, example 43), the title compound was prepared from Trans-2-[tert-Butoxycarbonylamino-(toluene-4-sulfonyl)-methyl]-cyclobutanecarboxylic acid methyl ester (17.7 g, 44.53 mmol), sodium borohydride (3.3 g, 83.74 mmol) and 8.2 g, (33.7 mmol, 73.4% yield) was obtained. MS (m/e): 244.0 (M+H+). (33.7 mmol, 73.4% yield) was obtained

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Trans-2-(tert-Butoxycarbonylamino-methyl)-cyclopropanecarboxylic acid ethyl ester (0.320 g, 1.3 mmol), in toluene (5 mL) at −78° C. a 1.2M solution of DIBAL-H (1.86 mL, 2.2 mmol) in toluene was added. The mixture was stirred at −78° C. until TLC after 0.5 h indicated completion of the reaction. A saturated solution of sodium tartrate was added and the water was extracted three times with dichloromethane. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated. The crude product was used without purification on the next step. MS (m/e): 200.3 (M+H+) completion of the reaction the water was extracted three times with dichloromethane The combined organic layers were washed with water and brine dried over magnesium sulfate filtered evaporated The crude product was used without purification on the next step

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

Procedure: Sodium Borohydride (2.3 g, 58.55 mol) was suspended in tetrahydrofuran (150 mL) and 4 mL of water was added. (13.3 g, 33.46 mmol) of trans-2-[tert-Butoxycarbonylamino-(toluene-4-sulfonyl)-methyl]-cyclopropanecarboxylic acid ethyl ester was added portionwise (0.8 g portions) and the temperature was kept to 18-30° C. After 1.5 h water (4 mL) and 0.4 g (10.15 mmol) of sodium borohydride were added again. The resulting mixture was quenched with ammonium chloride 2M (300 mL) and 100 mL of 1M K2CO3 and stirring was continued for 0.5 h. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (300 mL) and the combined organic layers were dried over MgSO4 and concentrated to dryness under vacuum and purified with column chromatography on silica with heptane/AcOEt (9/1) to obtain 7.5 g (92.1% yield) of the title compound. as a white solid. MS (m/e): 244.1 (M+H+) was kept to 18-30° C The resulting mixture was quenched with ammonium chloride 2M (300 mL) and 100 mL of 1M K2CO3 The organic layer was separated the aqueous phase was extracted with ethyl acetate (300 mL) the combined organic layers were dried over MgSO4 concentrated to dryness under vacuum purified with column chromatography on silica with heptane/AcOEt (9/1)

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

Procedure: According to the synthesis of Trans-2-(tert-Butoxycarbonylamino-methyl)-cyclopropanecarboxylic acid ethyl ester (intermediate L, example 43), the title compound was prepared from Trans-2-[tert-Butoxycarbonylamino-(toluene-4-sulfonyl)-methyl]-cyclobutanecarboxylic acid methyl ester (17.7 g, 44.53 mmol), sodium borohydride (3.3 g, 83.74 mmol) and 8.2 g, (33.7 mmol, 73.4% yield) was obtained. MS (m/e): 244.0 (M+H+). (33.7 mmol, 73.4% yield) was obtained

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

Procedure: Sodium Borohydride (2.3 g, 58.55 mol) was suspended in tetrahydrofuran (150 mL) and 4 mL of water was added. (13.3 g, 33.46 mmol) of trans-2-[tert-Butoxycarbonylamino-(toluene-4-sulfonyl)-methyl]-cyclopropanecarboxylic acid ethyl ester was added portionwise (0.8 g portions) and the temperature was kept to 18-30° C. After 1.5 h water (4 mL) and 0.4 g (10.15 mmol) of sodium borohydride were added again. The resulting mixture was quenched with ammonium chloride 2M (300 mL) and 100 mL of 1M K2CO3 and stirring was continued for 0.5 h. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (300 mL) and the combined organic layers were dried over MgSO4 and concentrated to dryness under vacuum and purified with column chromatography on silica with heptane/AcOEt (9/1) to obtain 7.5 g (92.1% yield) of the title compound as a white solid. MS (m/e): 244.1 (M+H+) was kept to 18-30° C The resulting mixture was quenched with ammonium chloride 2M (300 mL) and 100 mL of 1M K2CO3 The organic layer was separated the aqueous phase was extracted with ethyl acetate (300 mL) the combined organic layers were dried over MgSO4 concentrated to dryness under vacuum purified with column chromatography on silica with heptane/AcOEt (9/1)