Réaction #623912

Équation de réaction

mixture

(R,E)-2-fluoro-N-(1-methyl-5-(1-methylcyclopropyl)-2-((tetrahydrofuran-2-yl)methyl)-1H-pyrazol-3(2H)-ylidene)-5-(trifluoromethyl)benzamide

3-methylbutane-1,3-diol

sodium 2-methylpropan-2-olate

→

title compound

Rendement 54.4%

2-(3-hydroxy-3-methylbutoxy)-N-{(3E)-1-methyl-5-(1-methylcyclopropyl)-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-5-(trifluoromethyl)benzamide

Rendement 54.4%

Solvants

THF

H2O

Conditions de réaction

Traitement

1. 1
   Extractionextracted with EtOAc (2×)
2. 2
   SéchageThe combined organic extracts were dried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated
5. 5
   AutreThe residue was purified by column chromatography

Mode opératoire

A mixture of Example 68D (600 mg, 1.41 mmol), 3-methylbutane-1,3-diol (294 mg, 2.82 mmol) and sodium 2-methylpropan-2-olate (271 mg, 2.82 mmol) in THF (30 mL) was heated at 40° C. for 12 hours. The reaction mixture was diluted with H2O and extracted with EtOAc (2×). The combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 50% hexanes/EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N) to afford 391 mg (54%) of the title compound. 1H NMR (500 MHz, chloroform-d) δ ppm 0.76-0.83 (m, 2H) 0.89-0.98 (m, 2H) 1.31 (s, 6H) 1.34 (s, 3H) 1.69-1.82 (m, 2H) 1.81-1.90 (m, 1H) 1.96-2.11 (m, 3H) 3.66-3.80 (m, 2H) 3.83 (s, 3H) 4.15-4.32 (m, 4H) 4.52 (dd, J=14.49, 2.59 Hz, 1H) 5.62 (s, 1H) 6.98 (d, J=8.54 Hz, 1H) 7.03 (s, 1H) 7.53 (dd, J=8.54, 2.14 Hz, 1H) 8.30 (d, J=2.14 Hz, 1H); MS (DCI/NH3) m/z 510 (M+H)+.

Source