Reaktion #7756

Reaktionsgleichung

2,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-yl)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

sodium phenolate

→

desired product

Ausbeute 21.0%

2-(4-fluorophenyl)-6-hydroxy-3-(2-phenoxypyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Ausbeute 21.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooling bath is removed
2. 2
   SonstigeThe reaction is quenched with NH4Cl (sat. aq.) (500 μL)
3. 3
   EinengenThe reaction mixture is concentrated in vacuo
4. 4
   workup.ADDITIONthe residue diluted
5. 5
   WaschenThe solution is washed with water (20 mL)
6. 6
   ExtraktionThe combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL)
7. 7
   Sonstigedried
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated in vacuo
10. 10
    SonstigeThe crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate)

Vorschrift

A solution of 2,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methane-sulfonyl-pyrimidin-4-yl)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester, 35, (50 mg, 0.105 mmol) in THF (1 mL) is slowly cannulated into a solution of sodium phenolate in THF (1 mL) at 0° C. The cooling bath is removed and the reaction stirred at room temperature for 1 hour. The reaction is quenched with NH4Cl (sat. aq.) (500 μL). The reaction mixture is concentrated in vacuo and the residue diluted taken up in ethyl acetate (15 mL). The solution is washed with water (20 mL) and a 5% aqueous Na2CO3 (20 mL). The combined aqueous layers are extracted with ethyl acetate (25 mL) and brine (20 mL), dried, filtered and concentrated in vacuo. The crude material is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate) to afford 9 mg (21% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ8.43 (d, J=5.2 Hz, 1H), 7.46 (t, J=7.8 Hz, 2H), 7.31–7.27 (m, 3H), 7.19 (d, J=8.2Hz, 2H), 7.03 (t, J=8.6Hz, 2H), 6.80 (d, J=5.2 Hz, 1H), 5.41 (br s, 1H), 4.82 (m, 1H), 4.23 (d, J=12.4 Hz, 1H), 3.95–3.85 (m, 2H), 3.76 (dd, J=12.4, 4.4 Hz, 1H); HRMS m/z calcd for C22H18FN4O3 (MH+) 405.1363, found 405.1365.

Quelle