HCID 21975858, compound → 6-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline

Participants

Reaction Conditions

Reaction Steps

6-Bromo-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline (4.32 g, 11.8 mmol, 1 eq), NaOt-Bu (1.64 g, 17.11 mmol, 1.45 eq), Pd2(dba)3 (110 mg, 0.12 mmol, 0.01 eq) and BINAP (221 mg, 0.354 mmol, 0.03 eq) were combined in a round-bottomed flask and purged with nitrogen. 30 mL of dry toluene was added and the solution became red slurry. To this was added a solution of (2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl (2 g, 13 mmol, 1.1 eq) in 30 mL of dry toluene. The reaction mixture was heated to 85° C. and stirred overnight. The reaction mixture was cooled to rt and quenched with 50 mL of water. This was transferred to a separatory funnel along with 100 mL of brine. The organics were extracted with ethyl acetate (2×100 mL), where they were combined, dried over Na2SO4, concentrated under vacuum and purified by column chromatography on silica gel (200 g column; 50 mL/min; 5% MeOH in CH2Cl2), which afforded 4.02 g (78%) of the title compound as an orange solid.

Provenance & Evidence