Phenylacetyl chloride → 2-Tert-butoxy-2-[4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2-phenylacetyl)-5,7-dihydro-1,6-naphthyridin-3-yl]acetic acid

Participants

Reaction Steps

To a solution of 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (example 1) (9.2 mg, 0.021 mmol) in CH2Cl2 (5 mL) was added Et3N (8.98 μl, 0.064 mmol) followed by 2-phenylacetyl chloride (4.26 μl, 0.032 mmol) and the mixture stirred at room temperature. (Mixture became a clear, colorless solution within 30 min.) After 3 h, the solvent was removed and the residue was taken up in MeOH/DMF and purified by preparative HPLC (10% AcCN/90% H2O/0.1% NH4OAc, Sunfire 19×100 mm, C18, 5 μm). The product was dissolved in MeOH and repurified by preparative HPLC (10% AcCN/90% H2O/0.1% NH4OAc, Sunfire 19×100 mm, C18, 5 μm) to give 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2-phenylacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (1.3 mg, 10% yield) as a white solid. 1H NMR (500 MHz, CD3OD) δ ppm 7.38-7.60 (1H, m), 7.00-7.40 (7H, m), 6.97 (1H, d, J=7.02 Hz), 4.75-4.85 (1H, m), 4.35-4.47 (0.5H, m), 4.17-4.34 (1H, m), 3.98 (0.5H, d, J=16.48 Hz), 3.77-3.93 (1.5H, m), 3.57-3.77 (3H, m), 3.53 (0.5H, d, J=13.12 Hz), 1.22-1.42 (9H, m), 1.11-1.22 (3H, m), 0.87-1.04 (9H, m). LCMS (M+H) calcd for C33H40FN2O4: 547.29. found: 547.4.

Provenance & Evidence