Methyl 4-Formylbenzoate → (S)-4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid methyl ester

Participants

Reaction Steps

Add 4-formylbenzoic acid methyl ester (133 mg, 0.815 mmol) to a solution of (S)-(3,5-bis-trifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine (Example 3, Step 18) (150 mg, 0.272 mmol) in acetic acid (1 mL) and 1,2-dichloroethane (10 mL) at room temperature under nitrogen and stir for 2 h. Add sodium triacetoxy borohydride (231 mg, 1.08 mmol) and stir for 3 h. Dilute the mixture with methylene chloride (30 mL) and wash with saturated aqueous sodium bicarbonate solution (2×10 mL). Extract the combined aqueous washes with methylene chloride (20 mL) and wash the combined organic extracts with brined (20 mL) and dry over anhydrous sodium sulfate. Remove the solvents under reduced pressure and purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (1:2), to provide the title compound as a white solid (100 mg, 52%): mp 71-74° C. dec; 1H NMR (CDCl3, 300 MHz) δ 1.61-1.65 (m, 2H), 2.02-2.22 (m, 2H), 2.29 (s, 3H), 2.71-2.80 (m, 1H), 3.02-3.11 (m, 1H), 3.89 (s, 3H), 4.18 (s, 3H), 4.22-4.40 (m, 2H), 4.89-5.10 (m, 2H), 5.55-5.60 (m, 1H), 6.90 (s, 1H), 7.21 (s, 1 H), 7.45-7.49 (m, 2H), 7.65-7.70 (m, 2H), 7.75-7.80 (m, 1H), 7.97-7.81 (m, 2H); ESI MS m/z 701 [C32H29F9N6O2+H]+; HPLC 98.3%, tR 19.6 min.

Provenance & Evidence