Tetrahydrofuran → (Z)-methyl 4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate

HRID 1748827Notes

Reaction equation

HRID 1748827 reaction equation
[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1[CH:14]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[CH3:24])C=O.C1(P(=[CH:44][C:45]([O:47][CH3:48])=[O:46])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:49]1COCC1>>[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1/[C:14](/[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[CH3:24])=[CH:49]\[CH2:44][C:45]([O:47][CH3:48])=[O:46]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 17453Acetic acid, 2-(triphenylphosphoranylidene)-, methyl esterHCID 867241492-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-2-(4-chloro-2-methylphenyl)acetaldehyde

Product 1

HCID 86724150(Z)-methyl 4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoateYield 89%

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-2-(4-chloro-2-methylphenyl)acetaldehyde (13 g, 36.1 mmol) in THF (200 mL) was added methyl (triphenylphosphoranylidene)acetate (24.13 g, 72.2 mmol). The mixture was stirred at about 60° C. for about 16 h then cooled in an ice bath. The solids were removed by filtration then filtrate was concentrated in vacuo. The residue was purified by column chromatography (SiO2, 0-20% EtOAc/heptanes) to give (Z)-methyl 4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate (13.34 g, 89%): LC-MS (Table 1, Method g) Rt=2.62 min, m/z 416/418 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 8.41-8.38 (m, 1H), 7.81-7.70 (m, 2H), 7.27-7.20 (m, 1H), 7.19-7.17 (m, 1H), 7.09-7.05 (m, 1H), 7.02-6.99 (m, 1H), 5.91 (t, J=7.3 Hz, 1H), 3.91 (s, 3H), 3.52 (s, 3H), 3.11-2.96 (m, 2H), 2.34 (s, 3H).

Workup

  1. temperaturethen cooled in an ice bath
  2. customThe solids were removed by filtration
  3. concentrationfiltrate was concentrated in vacuo
  4. customThe residue was purified by column chromatography (SiO2, 0-20% EtOAc/heptanes)

Sources & evidence

ORD record
ord-30d47684f3dc4553aee87aff1d40ba93
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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