Tributylphosphine → (3S)-3-[1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Purge nitrogen through a solution of (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (S-1) (0.5 g, 1.94 mmol) and 6-methoxy-2-methyl-pyridin-3-ol (0.41 g, 2.91 mmol) in toluene (10 mL) at room temperature for 10 minutes. Add tri-n-butylphosphine (0.73 mL, 2.91 mmol) followed by azodicarboxylic acid dipiperidide (0.59 mg, 2.91 mmol). Heat the reaction mixture to 70° C., and stir over night. Cool the mixture to room temperature and pour onto saturated aqueous NaHCO3 (50 mL). Extract with ethyl acetate (2×), combine the organic extracts and dry (Na2SO4), filter and concentrate. Purify the crude residue by silica gel chromatography eluting with 0-20% ethyl acetate in hexanes to afford (3S)-3-[1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (S-2) (101 mg, 13%). The deprotection and the L-tartarte formation are performed essentially as in EXAMPLE 1 to afford the title compound. MS (m/z)=279 [M+1]

Provenance & Evidence