tert-butyl 5-amino-1,3,3a,4,5,6,7,7a-octahydroisoindole-2-carboxylate

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

Procedure: To a solution of 2,4,5-trichloropyrimidine (0.60 g, 3.27 mmol) and tert-butyl 5-aminohexahydro-1H-isoindole-2(3H)-carboxylate (2.79 g, 11.61 mmol) in EtOH (10 mL) was added Et3N (1.30 g, 12.84 mmol). After addition, the reaction mixture was stirred at rt overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5) to give the title compound as a pale yellow solid (1.60 g, 100%). After addition concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5)

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

Procedure: To a solution of tert-butyl 5-oxohexahydro-1H-isoindole-2(3H)-carboxylate (11.97 g, 50 mmol) in EtOH (100 mL) were added a solution of NH3 in MeOH (7 M, 100 mL, 700 mmol) and Ti(OiPr)4 (28.42 g, 100 mmol). After addition, the reaction mixture was stirred at rt overnight and NaBH4 (3.78 g, 100 mmol) was added portionwise, then the resulting mixture was stirred at rt for another 5 h. The reaction was quenched with water (100 mL), stirred at rt for 1 h and filtered. The filter cake was washed with DCM (100 mL×3) and the filtrate was concentrated in vacuo. The residue was dissolved in a mixture of EtOAc (100 mL) and water (100 mL), and extracted with EtOAc (250 mL×3). The combined organic phases were washed with brine (250 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the title compound as brown oil (12.02 g, 100%). After addition the resulting mixture was stirred at rt for another 5 h The reaction was quenched with water (100 mL) stirred at rt for 1 h filtered The filter cake was washed with DCM (100 mL×3) the filtrate was concentrated in vacuo The residue was dissolved in a mixture of EtOAc (100 mL) and water (100 mL) extracted with EtOAc (250 mL×3) The combined organic phases were washed with brine (250 mL) dried over anhydrous Na2SO4 filtered concentrated in vacuo