Acetic Acid → HCID 24905914, compound

Participants

Reaction Conditions

Reaction Steps

To 30 mg (0.055 mmol) of amine 7-2 in MeOH was added 30 μL (0.55 mmol) of HOAc, 33 μL (0.17 mmol) of (1-ethoxycyclopropoxy)trimethylsilane, 10 mg (0.17 mmol) of NaCNBH3 and 100 mg of 4 Å molecular sieves. The mixture was then heated at 100° C. for 10 min in a microwave reactor. After cooling to room temperature, ˜500 μL of trifluoroacetic acid was added and the mixture was stirred for 1 h. The reaction was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with water, brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with 20:1:1 EtOH/NH4OH/H2O in EtOAc to provide 15-1 as a white solid. Data for 15-1: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (m, 3H), 6.3 (s, 1H), 5.45 (m, 1H), 4.8 (m, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 4.0 (m, 1H), 3.75 (m, 1H), 3.15 (m, 2H), 2.9 (s, 3H), 2.3 (m, 2H), 1.9-1.6 (m, 5H), 0.5-0.4 (m, 4H) ppm. HRMS (ES) calc'd M+H for C27H31F2N3O2: 468.2457. Found: 468.2438. Resolution of the enantiomers was carried out chromatographically using a Chiralpak AD© 10×50 cm column with 15% isopropanol in hexanes (with 0.1% diethylamine) at 150 mL/min. Analytical HPLC analysis of the eluent on a 4×250 mm Chiralpak AD® column with 15% isopropanol in hexanes (with 0.1% diethylamine) at 1 mL/min indicated that inactive enantiomer has Rt=7.05 min and the active enantiomer has Rt=8.17 min.

Provenance & Evidence