Phosphorus oxychloride → Methyl 4-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)benzoate

HRID 81061Notes

Reaction equation

HRID 81061 reaction equation
[C:1]([C:3]1[C:4](=O)[CH:5]=[C:6]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=2)[NH:7][C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)#[N:2].P(Cl)(Cl)([Cl:35])=O>>[Cl:35][C:4]1[C:3]([C:1]#[N:2])=[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:11][CH:10]=2)[N:7]=[C:6]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=2)[CH:5]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 66927073Methyl 4-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)benzoate

Product 1

HCID 66927119Methyl 4-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)benzoateYield 89%

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 4-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)benzoate (598.2 mg, 1.416 mmol) and phosphoryl trichloride (12 mL) was heated to 90° C. for 1 h then concentrated. The residue was dissolved in dichloromethane, washed with water and concentrated. Silica gel chromatography, eluting with 0-20% ethyl acetate in hexanes, gave methyl 4-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)benzoate as white solid (0.5582 g, 89% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.19 (4H, s), 8.01-8.06 (2H, m), 7.89 (1H, s), 7.38-7.44 (2H, m), 7.20 (1H, t, J=7.40 Hz), 7.10-7.17 (4H, m), 3.97 (3H, s), MS (ES+) m/z: 441 (M+H); LC retention time: 4.333 min (analytical HPLC Method A).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washwashed with water
  4. concentrationconcentrated
  5. washSilica gel chromatography, eluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-77f4a299a1794e088bf1f75cc02ba00c
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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