Diisobutylaluminumhydride → HCID 68380623, compound

Participants

Reaction Steps

Diisobutylaluminum hydride (1.5 M in toluene, 1.63 mL, 2.44 mmol) was added to a solution of (2S)-1-[4-fluoro-2-(1,1,1-trifluoropropan-2-yl)phenoxy]propan-2-amine (P13) (fractions that were enriched in the lower Rf diastereomer were used, see step 4 of Preparation 13; 324 mg, 1.22 mmol) in tetrahydrofuran (5 mL). After the vigorous bubbling subsided, the reaction mixture was stirred for 2 hours at room temperature. 7-(4-Methyl-1H-imidazol-1-yl)-3,4-dihydropyrido[2,1-c][1,4]oxazine-1,6-dione (P14) (299.7 mg, 1.222 mmol) was added, and the reaction mixture was heated to 60° C. for 24 hours. It was then cooled to room temperature, carefully quenched with 1 M aqueous sodium hydroxide solution, and extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the product as a sticky orange-tan oil. This was used in the following step without additional purification. Yield: 430 mg, 0.84 mmol, 69%. LCMS m/z 511.3 (M+1). On large scale, use of diisobutylaluminum hydride was less successful; in this case, simply dissolving P13 and P14 in methanol, boiling the solution down to a thick homogeneous oil and heating at 110° C. provided superior results.

Provenance & Evidence