Sodium Hydroxide → (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid

HRID 1748828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1748828
[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:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[CH3:28])=[CH:15]\[CH2:16][C:17]([O:19]C)=[O:18].[OH-].[Na+]>O1CCOCC1>[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:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[CH3:28])=[CH:15]\[CH2:16][C:17]([OH:19])=[O:18]

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 86724150(Z)-methyl 4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate

Produkt 1

HCID 86724151(Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acidAusbeute 95,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of (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, 32.0 mmol) in dioxane (150 mL) was added 2 N aqueous NaOH (32 mL, 64 mmol). The mixture was stirred at rt for about 16 h then partitioned between EtOAc (300 mL) and 10% citric acid (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (300 mL). The combined organic layers were washed with water (300 mL) followed by brine (300 mL) then concentrated in vacuo. The residue was triturated in Et2O to give (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid (12.31 g, 95%) as an off-white solid: LC-MS (Table 1, Method g) Rt=2.20 min, m/z 402/404 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 12.18 (s, 1H), 8.42-8.39 (m, 1H), 7.80-7.68 (m, 2H), 7.26-7.19 (m, 1H), 7.16 (d, J=2.2 Hz, 1H), 7.08-7.04 (m, 1H), 7.01-6.97 (m, 1H), 5.91 (t, J=7.2 Hz, 1H), 3.92 (s, 3H), 2.95 (s, 2H), 2.34 (s, 3H). To a suspension of (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoic acid (12.31 g, 30.6 mmol) in THF (50 mL) was added 2-methylpropan-2-amine (6.46 mL, 61.2 mmol). The mixture was stirred at rt for about 10 min then concentrated in vacuo to give 2-methylpropan-2-aminium (Z)-4-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-(4-chloro-2-methylphenyl)but-3-enoate (14.40 g, 95%): LC-MS (Table 1, Method g) Rt=2.20 min, m/z 402/404 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 8.41-8.38 (m, 1H), 7.78-7.67 (m, 2H), 7.24-7.17 (m, 1H), 7.13 (d, J=2.1 Hz, 1H), 7.05-7.01 (m, 1H), 6.99-6.96 (m, 1H), 6.01 (t, J=7.1 Hz, 1H), 3.91 (s, 3H), 2.81-2.59 (m, 2H), 2.32 (s, 3H), 1.16 (s, 9H).

Aufarbeitung

  1. customthen partitioned between EtOAc (300 mL) and 10% citric acid (200 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (300 mL)
  4. washThe combined organic layers were washed with water (300 mL)
  5. concentrationthen concentrated in vacuo
  6. customThe residue was triturated in Et2O

Quellen und Nachweise

ORD-Eintrag
ord-9fbdf31fa88644ce8224b3fbd2ec1d3d
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150592B2

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