Reaktion #160204

Reaktionsgleichung

(4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt

2,2,2-trifluoroethyl trifluoromethanesulfonate

NaHCO3

→

(4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone

Ausbeute 9.0%

Lösungsmittel

EtOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to room temperature
2. 2
   Sonstigemicrofiltered and purified by Waters mass
3. 3
   Einengen(10-99% ACN/H2O (5 mM HCl)) and concentrated in vacuo

Vorschrift

A mixture of (4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt (32 mg, 0.07 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (17 μL, 0.11 mmol) and NaHCO3 (24 mg, 0.28 mmol) in anhydrous EtOH (800 μL) was heated at 80° C. in a sealed vial for 18 hours. The reaction mixture was allowed to cool to room temperature, microfiltered and purified by Waters mass directed LC/MS: (10-99% ACN/H2O (5 mM HCl)) and concentrated in vacuo to yield (4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (3 mg, 9%) as a white solid. ESI-MS m/z calc. 495.5. Found 496.7 (M+1)+; Retention time: 1.99 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.27-7.13 (m, 2H), 6.96 (d, J=9.0 Hz, 1H), 6.82 (d, J=1.2 Hz, 1H), 4.86 (dd, J=12.0, 4.7 Hz, 1H), 4.71-4.54 (m, 1H), 3.32-3.14 (m, 5H), 3.07 (dd, J=11.5, 2.6 Hz, 1H), 2.90-2.83 (m, 1H), 2.70 (dd, J=18.3, 7.2 Hz, 1H), 2.41-2.23 (m, 6H), 2.13 (s, 3H), 1.64-1.39 (m, 3H), 1.29 (d, J=6.0 Hz, 6H).

Quelle