2-Mercaptobenzoic Acid → HCID 58815986, compound

Participants

Reaction Steps

Bis(dibenzylideneacetone)palladium (398 mg) was added to a solution of 1,4-bis(diphenylphosphino)butane (295 mg) in THF (7.3 mL) under nitrogen at room temperature for 10 minutes. The resulting Pd-catalyst was transferred to the solution of 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.6 g, Ex. 58) and thiosalicylic acid (1.71 g) in THF (40 mL) via a syringe. The reaction was stirred under nitrogen at room temperature for overnight. The reaction mixture was concentrated under vacuum. EtOAc (75 mL) was added to the residue, followed by the addition of 1 N aqueous HCl (110 mL). The EtOAc layer and acidic water layer were separated. The acidic water layer was extracted with EtOAc (50 mL×2). The acidic water layer was neutralized with saturated NaHCO3 solution to pH≅8 and then extracted with n-butanol (75 mL×3). The combined n-butanol layer was washed with water (60 mL) and concentrated to give crude product, 1-{3-[(R)-((2S,5R)-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.0 g). 1H NMR (300 MHz, CD3OD) δ 7.55-7.37 (m, 3H), 7.27 (m, 1H), 7.18 (dd, J=8.0, 8.0, 1H), 6.71 (m, 2H), 6.61 (s, 1H), 5.36 (s, 1H), 4.44 (m, 1H), 4.14 (q, J=7.0 Hz, 2H), 3.68 (m, 1H), 3.08 (m, 2H), 2.89 (m, 2H), 2.65 (m, 2H), 2.46 (m, 1H), 2.00 (m, 1H), 1.84 (m, 1H), 1.76-1.45 (m, 3H), 1.25 (t, J=7.0 Hz, 3H), 1.21 (d, J=6.0 Hz, 3H), 0.96 (d, J=6.5, 3H).

Provenance & Evidence