Phosphorus oxychloride → N-[4-(Cyano-dimethyl-methyl)-2-fluoro-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide

HRID 1297588Notes

Reaction equation

HRID 1297588 reaction equation
[C:1]([C:4]([C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13](=[O:28])[C:14]2[CH:19]=[CH:18][CH:17]=[N:16][C:15]=2[O:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[C:9]([F:31])[CH:8]=1)([CH3:6])[CH3:5])(=O)[NH2:2].P(Cl)(Cl)(Cl)=O>>[C:1]([C:4]([CH3:6])([CH3:5])[C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13](=[O:28])[C:14]2[CH:19]=[CH:18][CH:17]=[N:16][C:15]=2[O:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[C:9]([F:31])[CH:8]=1)#[N:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 10295972N-[4-(1-Carbamoyl-1-methyl-ethyl)-2-fluoro-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide

Product 1

HCID 17832827N-[4-(Cyano-dimethyl-methyl)-2-fluoro-benzyl]-2-(4-fluoro-phenoxy)-nicotinamideYield 82.1%

Conditions

Temperature
90 °C

Procedure

To N-[4-(1-Carbamoyl-1-methyl-ethyl)-2-fluoro-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide (3.00 g) in a 50 mL flask was added phosphorous oxychloride (3.29 mL). The solution was heated for 1 h at 90° C. The solution was then cooled in an ice bath, poured over satd. aq. sodium carbonate (50 mL), then extracted with ethyl acetate (4×100 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo, yielding the title compound (2.36 g).

Workup

  1. temperatureThe solution was then cooled in an ice bath
  2. additionpoured over satd
  3. extractionaq. sodium carbonate (50 mL), then extracted with ethyl acetate (4×100 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ebaace09f7c54565877232c0ad3c12a7
Source dataset
uspto-grants-2007_07
Patent number
US07250518B2

Reaction notes

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