Hydrochloric Acid → ((R)-2-Hydroxymethyl-piperazin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochloride

関与物質

反応手順

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 4-N-Boc-2-(R)-hydroxymethyl-piperazine by the method described in Example 2 Method B. The reaction mixture was evaporated to a solid, triturated and filtered with the aid of water, then washed with a 1 N aqueous hydrochloric acid solution followed by water. The solid was air dried afford intermediate N-Boc protected product as a colorless solid (102 mg, 86%). The Boc-protected intermediate was dissolved in a 4 N solution of hydrogen chloride in 1,4,-dioxane (2 mL) and stirred for 2 hr, after which time the reaction mixture was evaporated to approximately ¼ volume and diluted with ethyl ether (4 mL). The resulting solids were filtered and air dried to afford product as a colorless solid (85 mg, 83% overall). 1H NMR (D2O) 2.17 (s, 3H), 3.26-3.46 (m, 3H), 3.60-3.80 (m, 3H), 4.00-4.04 (m, 1H), 4.48 (dd, J=12.7, 5.3, 1H), 4.60 (obs dd, J=13.2, 3.5, 1H), 7.46 (d, J=4.3, 1H), 7.82 (d, J=4.0, 1H). 19F NMR −63.5. LC/MS 3.89 min, [M+1]+ 376.

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