2,4-Dichlorobenzaldehyde → (3S)-1-(5-bromopyrimidin-2-yl)-N-[(2,4-dichlorophenyl)methyl]pyrrolidin-3-amine

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Reaction Steps

Combine (S)-1-(5-bromopyrimidin-2-yl)-pyrrolidine-3-amine (10.0 g, 35.84 mmol) and 30% aqueous sodium hydroxide (1.18 equiv., 4 mL) in water (30 mL), THF (75 mL), and toluene (75 mL). Separate the layers, extract the aqueous layer with 1:1 THF:toluene (50 mL). Combine the organic layers and extract with water (10 mL). Evaporate the organic layer at reduced pressure to give a residue. Combine the residue and toluene (75 mL) and evaporate at reduced pressure to give a residue. Again, combine the residue and toluene (75 mL) and evaporate at reduced pressure to give a residue Combine the residue and toluene (12.9 g) and dry THF (53.2 g), add 2,4-dichlorobenzaldehyde (0.94 equivalent, 33.6 mmol, 6.0 g), and stir. After 1 hour, add sodium triacetoxyborohydride (65.9 mmol, 2.5 equiv., 14.4 g) in 5 portions over about 50 minutes. After 22 hours, slowly add water (16 mL), Stir for 2 hours and then basify to pH=14 by addition of 30% aqueous sodium hydroxide (20 mL). Separate the aqueous layer and extract with 1/1 toluene/THF (120 mL). Combine the organic layers and extract with water (30 mL). Evaporate the solvents at reduced pressure to give a residue. Combine the residue and isopropanol (130 mL) and evaporate at reduced pressure to give a residue. Twice more, combine the residue and isopropanol (130 mL) and evaporate at reduced pressure to give a mass of about 90 g. Slowly cool to room temperature and agitate for about 3 hours to give a solid. Collect the solid by filtration, rinse with isopropanol (10 mL), and dry at 40° C. under vacuum for 15 hours to give the title compound.

Provenance & Evidence