(3S)-3-(4-bromoanilino)butanamide

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3S)-3-[(4-bromophenyl)amino]butanenitrile (for a preparation see Intermediate 32) (17.3 g, 72.4 mmol) was taken up in Toluene (500 ml) and H2SO4 (19.28 ml, 362 mmol) added. The biphasic mixture was stirred at 60° C. After two hours, only a small amount of SM remained by LCMS so the reaction was diluted with water (500 ml) and the phases separated. The aqueous phase was basified with 10N NaOH and extracted with EtOAc (2×750 ml). The combined organics were dried with Na2SO4, filtered and concentrated to yield the product as a cream solid (17.5 g). LCMS (Method B): Rt=0.77, MH+=257 the phases separated extracted with EtOAc (2×750 ml) The combined organics were dried with Na2SO4 filtered concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3S)-3-[(4-bromophenyl)amino]butanenitrile (for a preparation see Intermediate 32) (17.3 g, 72.4 mmol) was taken up in Toluene (500 ml) and H2SO4 (19.28 ml, 362 mmol) added. The biphasic mixture was stirred at 60° C. After two hours, only a small amount of SM remained by LCMS so the reaction was diluted with water (500 ml) and the phases separated. The aqueous phase was basified with 10N NaOH and extracted with EtOAc (2×750 ml). The combined organics were dried with Na2SO4, filtered and concentrated to yield the product as a cream solid (17.5 g). LCMS (Method B): Rt=0.77, MH+=257 the phases separated extracted with EtOAc (2×750 ml) The combined organics were dried with Na2SO4 filtered concentrated

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

Procedure: (3S)-3-[(4-bromophenyl)amino]butanamide (for a preparation see Intermediate 13, 24.9 g, 97 mmol) was taken up in Ethyl acetate (850 mL) and cooled to <−9° C. (internal). Isopropyl chloroformate (116 mL, 116 mmol, Aldrich) was added followed by slow addition of Lithium tert-butoxide (18.61 g, 232 mmol) in Tetrahydrofuran (THF) (232 mL) keeping the temperature below 0° C. The reaction was stirred for 30 mins then checked by LCMS which showed a complete reaction. The mixture was partitioned between EtOAc (1000 ml) and 2N HCl (2000 ml). The organic layer was washed with brine (2000 ml) and then dried with Na2SO4, filtered and concentrated to yield the product as a brown oil (17.9 g) LCMS (Method B): Rt=1.09, MH+=343 cooled to <−9° C. (internal) the temperature below 0° C a complete reaction The mixture was partitioned between EtOAc (1000 ml) and 2N HCl (2000 ml) The organic layer was washed with brine (2000 ml) dried with Na2SO4 filtered concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3S)-3-[(4-bromophenyl)amino]butanenitrile (for a preparation see Intermediate 12) (17.3 g, 72.4 mmol) was taken up in Toluene (500 ml) and H2SO4 (19.28 ml, 362 mmol) added. The biphasic mixture was stirred at 60° C. After two hours, only a small amount of SM remained by LCMS so the reaction was diluted with water (500 ml) and the phases separated. The aqueous phase was basified with 10N NaOH and extracted with EtOAc (2×750 ml). The combined organics were dried with Na2SO4, filtered and concentrated to yield the product as a cream solid (17.5 g). LCMS (Method B): Rt=0.77, MH+=257 the phases separated extracted with EtOAc (2×750 ml) The combined organics were dried with Na2SO4 filtered concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3S)-3-[(4-Bromophenyl)amino]butanenitrile (for a preparation see Intermediate 104) (17.3 g, 72.4 mmol) was taken up in toluene (500 ml) and H2SO4 (19.28 ml, 362 mmol) added. The biphasic mixture was stirred at 60° C. After two hours, only a small amount of starting material remained by LCMS so the reaction was diluted with water (500 mL) and the phases separated. The aqueous phase was basified with 10N NaOH and extracted with EtOAc (2×750 mL). The combined organics were dried with Na2SO4, filtered and concentrated to yield the product as a cream solid (17.5 g). the phases separated extracted with EtOAc (2×750 mL) The combined organics were dried with Na2SO4 filtered concentrated