Ethanol → HCID 9814205, compound

Participants

Reaction Steps

N-[(2S)-6-Ethoxy-2,3-dihydro-1-oxo-1H-inden-2-yl]-2,2,2-trifluoroacetamide (V, EXAMPLE 4, 4.13 g, 15 mmol) is suspended in ethanol (45 ml) and cooled to −15°. Sodium borohydride (2.83 g, 75 mmol, 5 equiv.) is added and the reaction mixture gradually warmed to 20-25° overnight. The reaction mixture is concentrated to dryness and then suspended in acetonitrile (105 ml). Sodium phosphate tribasic (8.12 g, 49.5 mmol, 3.3 equivalents) is added and the mixture heated to 40°. n-Propylbromide (12.26 ml, 135 mmol, 9 equivalents) is added and reaction is heated to 65°. Heating is continued for 48 hr. The reaction mixture is filtered and the filtrate concentrated. The concentrate is partitioned in methyl t-butyl ether (100 ml) and sodium hydroxide (1 M, 50 ml). The organic layer is collected and acidified with hydrochloric acid (3 M, 50 ml). The aqueous phase is collected and the pH is adjusted to 13 using sodium hydroxide (50%, 25 ml). The product is extracted into methyl t-butyl ether (100 ml) and concentrated to give the title compound. TLC Rf=0.9 (ammonium hydroxide/methanolnmethylene chloride. 1.5/13.5/85); NMR δ7.04, 6.90, 6.79, 5.04, 4.01, 3.39, 2.87, 2.72, 2.59-2.48, 1.54-1.48, 1.39 and 0.90; CMR δ158.4, 144.2, 131.5, 125.6, 115.4, 109.2, 77.3, 73.2, 63.6, 53.6, 29.9, 21.1, 14.8, 11.9; MS (CI, NH3) m/z (relative intensity) 278 (100), 248 (70), 236 (20).

Provenance & Evidence