Tetrahydrofuran → HCID 25211286, compound

Participants

Reaction Steps

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and (R)-(+)-3-hydroxypiperidine hydrochloride by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine (containing and additional 1.1 eq. to neutralize the piperidinyl hydrochloride salt) and piperidine derivative. The reaction mixture was evaporated to an oil and partitioned between EtOAc (5 mL) and water (5 mL). The organic fraction was further washed with brine (2×5 mL), dried over MgSO4, filtered, and evaporated to an oil. The crude product was then chromatographed on silica gel with EtOAc/hexanes (50 then 75 then 100%) as eluant to afford product as a colorless solid (41 mg, 45%). 1H NMR (CDCl3) 1.56-1.62 (m, 1H), 1.62-1.80 (m, 1H), 1.83-2.10 (m, 2H), 2.36 (d, J=1.3, 3H), 2.86 (br, 1 H), 3.50-3.76 (m, 4H), 3.82-3.98 (m, 2H), 7.39 (br d, J=4.0, 1H), 7.44 (d, J=4.0, 1H). 13C NMR 7.9, 22.6, 32.5, ˜48 (br), ˜52 (br), 66.2, 114.7, 118.7 (q, J=271), 128.0, 129.6, 131.3, 140.1, 155.2 (q, J=40), 157.9, 163.5. 19F NMR −63.2. LC/MS 5.65 min, [M+1]+ 361.

Provenance & Evidence