Reaktion #496574

Reaktionsgleichung

K2CO3

(3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester

2,4-pentanedione

2-fluoro-4-nitrobenzyl bromide

→

[3,5-dimethyl-1-(2-fluoro-4-nitrobenzyl)-1H-pyrazol-4-yl]acetic acid tert-butyl ester

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe solid is filtered off
2. 2
   Sonstigethe solvent is removed by evaporation
3. 3
   workup.DISSOLUTIONThe residue is dissolved in dichloromethane/water
4. 4
   ExtraktionAfter extraction with dichloromethane the organic layer
5. 5
   Trocknenis dried over MgSO4
6. 6
   Sonstigeevaporated under reduced pressure
7. 7
   SonstigeThe residue is purified by MPLC (cyclohexane/ethyl acetate 7:3, silicagel 60)

Vorschrift

To a solution of (3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester (10 g, 47.6 mmol, preparation according to WO2007/141267 by using 2,4-pentanedione instead of 3,5-heptanedione) and 2-fluoro-4-nitrobenzyl bromide (11.2 g, 47.9 mmol) in acetonitrile (150 mL) is added K2CO3 (6.615 g, 47.9 mmol) and the mixture is stirred for 24 hours at room temperature. The solid is filtered off and the solvent is removed by evaporation. The residue is dissolved in dichloromethane/water. After extraction with dichloromethane the organic layer is dried over MgSO4 and evaporated under reduced pressure. The residue is purified by MPLC (cyclohexane/ethyl acetate 7:3, silicagel 60) to yield 13.6 g of [3,5-dimethyl-1-(2-fluoro-4-nitrobenzyl)-1H-pyrazol-4-yl]acetic acid tert-butyl ester (ESI mass spectrum: [M+H]+=364 TLC: Rf=0.23 (cyclohexan/ethyl acetate 7:3, solicagel 60 F254)). b) To a solution of [3,5-dimethyl-1-(2-fluoro-4-nitrobenzyl)-1H-pyrazol-4-yl]acetic acid tert-butyl ester (13.6 g, 37.4 mmol) in methanol (250 mL) is added Raney nickel (6 g) and the mixture is hydrogenated at 50 psi and 50° C. for 12 hours. The catalyst is filtered off and the filtrate is concentrated under reduced pressure to yield 11.6 g of the title compound (ESI mass spectrum: [M+H]+=334; TLC: Rf=0.53 (dichloromethane/methanol 95:5, silicagel 60 F254)).

Quelle