Reaktion #659467

Reaktionsgleichung

THF

piperidine

5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

4-hydroxy-4-trifluoromethyl-piperidine

→

product

Ausbeute 49.0%

(4-Hydroxy-4-trifluoromethyl-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]methanone

Ausbeute 49.0%

Lösungsmittel

triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was evaporated to a solid
2. 2
   Sonstigetriturated
3. 3
   Filtrationfiltered with the aid of water
4. 4
   Waschenwashed with a 1 N aqueous hydrochloric acid solution
5. 5
   Sonstigedried
6. 6
   Sonstigechromatographed on silica gel with EtOAc/hexanes (50%) as eluant

Vorschrift

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 4-hydroxy-4-trifluoromethyl-piperidine 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 and piperidine derivative. 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 and then chromatographed on silica gel with EtOAc/hexanes (50%) as eluant to afford product as a colorless solid (53 mg, 49%). 1H NMR (DMSO-d6) 1.70-1.72 (m, 4H), 2.34 (d, J=1.8, 3H), 3.24 (br, 2H), 4.19 (br, 2H), 6.17 (s, 1H), 7.56 (d, J=4.0, 1H), 7.65 (d, J=4.0, 1H). 19F NMR −83.5, −63.1. LC/MS 6.40 min, [M+1]+ 429.

Quelle