Methyl chloro[2-(4-fluorophenyl)hydrazinylidene]acetate → 1-(4-fluoro-phenyl)-4-isopropyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester

HRID 268631Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:15])[C:4](=[N:6][NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)Cl.[CH2:16]([O:23][C:24](=[O:30])[CH:25]=[CH:26][CH:27]([CH3:29])[CH3:28])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCOCC1>[CH3:1][O:2][C:3]([C:4]1[CH:26]([CH:27]([CH3:29])[CH3:28])[CH:25]([C:24]([O:23][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:30])[N:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:6]=1)=[O:15]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of [(4-fluoro-phenyl)-hydrazono]-chloroacetic acid methyl ester (20.93 g, 90.8 mmol) and 4-methyl-pent-2-enoic acid benzyl ester (18.54 g, 90.8 mmol) in dioxane (400 mL) at 25° C. was added Ag2CO3 (63.0 g, 227 mmol; commercially available from Sigma Aldrich). The reaction was protected from light and stirred at 25° C. for 48 hr. Subsequently, the reaction mixture was filtered through a pad of celite and the filtrate was concentrated. The crude product mixture was subjected to silica gel chromatography (5-20% EtOAc/Hex) to afford 1-(4-fluoro-phenyl)-4-isopropyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester in approximately 90% purity (29.3 g, 73%):: H-NMR (CDCI3) δ 7.30-7.24 (m, 3 H), 7.15-7.12 (m, 2 H), 7.01-6.96 (m, 2 H), 6.93-6.88 (m, 2 H), 5.14 (d, 1 H), 4.58 (d, 1 H), 3.83 (s, 3 H), 3.51-3.49 (m, 1 H), 2.40-2.36 (m, 1 H), 1.00 (d, 3 H), 0.69 (d, 3 H).

Workup

filtrationSubsequently, the reaction mixture was filtered through a pad of celite
concentrationthe filtrate was concentrated

Sources & evidence

ORD record: ord-d6e8bce58d1a43da8cbb25da57333df3
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07446121B2

Reaction notes

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