Dimethylformamide → ethyl 4-iodo-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate

Reaction equation

[I:1][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][NH:5][C:6]=1[CH3:7].[H-].[Na+].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20](Cl)=[CH:19][CH:18]=1.[CH3:24]N(C=O)C>>[I:1][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][N:5]([CH2:24][C:20]2[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=2)[C:6]=1[CH3:7]

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 121674-Chloroanisole

HCID 24758Sodium hydride

HCID 60136608ethyl 4-iodo-5-methyl-1H-pyrazole-3-carboxylate

Product 1

HCID 117702672ethyl 4-iodo-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylateYield 57%

Procedure

To a stirred solution of ethyl 4-iodo-5-methyl-1H-pyrazole-3-carboxylate (Step 1.1) (7.60 g, 27.1 mmol) in DMF (50 mL) under Ar was added NaH (1.302 g, 32.6 mmol) at 0° C. After 15 min, 4-methoxyphenyl chloride (3.70 mL, 27.1 mmol) was added. The reaction mixture was stirred for 1 hr at rt, quenched with a saturated aqueous solution of NaHCO3 (100 mL) and extracted with EtOAc (100 mL). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 (100 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc 5-40%) to afford the title product (6.23 g, 15.57 mmol, 57% yield) as a colorless oil. tR: 5.24 min (HPLC 1); tR: 1.12 min (LC-MS 2); ESI-MS: 401 [M+H]+ (LC-MS 2); Rf=0.66 (hexane/EtOAc 1:1).