Tributylphosphine → HCID 72319396, compound

Participants

Reaction Conditions

Reaction Steps

Bubble nitrogen through a solution of 3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (D1) (600 mg, 2.33 mmol) and 2-chloro-5-hydroxy-pyridine (0.451 g, 3.50 mmol) in toluene (10 mL) at room temperature for 10 minutes. Add tri-n-butylphosphine (0.872 mL, 3.50 mmol) followed by azodicarboxylic acid dipiperidide (0.882 g, 3.50 mmol). Heat the reaction mixture to 70° C., and stir over night. Add additional 3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (D1) (600 mg, 2.33 mmol), tri-n-butylphosphine (0.872 mL, 3.50 mmol) and azodicarboxylic acid dipiperidide (0.882 g, 3.50 mmol). Continue to stir at 70° C. for 3 hours. Cool the mixture to room temperature and pour into saturated aqueous NaHCO3. Extract with ethyl acetate (2×), combine the organic extracts, dry (Na2SO4), filter and concentrate. Purify the crude residue by silica gel chromatography eluting with 0-20% ethyl acetate in hexanes to afford 180 mg of 3-[1-(6-chloro-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (D2) for chiral separation.

Provenance & Evidence