5-Amino-2-chloro-4-fluorophenol → N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3-(1-cyano-1-methylethyl)benzamide

HRID 1800519Notes

Reaction equation

HRID 1800519 reaction equation
[NH2:1][C:2]1[C:3]([F:10])=[CH:4][C:5]([Cl:9])=[C:6]([OH:8])[CH:7]=1.C(=O)([O-])O.[Na+].[C:16]([C:18]([C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24](Cl)=[O:25])([CH3:20])[CH3:19])#[N:17]>O1CCCC1>[Cl:9][C:5]1[C:6]([OH:8])=[CH:7][C:2]([NH:1][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][CH:29]=[C:21]([C:18]([C:16]#[N:17])([CH3:19])[CH3:20])[CH:22]=2)=[C:3]([F:10])[CH:4]=1

Participants

5

Reactant 3

HCID 1586545-Amino-2-chloro-4-fluorophenolHCID 516892Sodium BicarbonateHCID 866319813-(1-Cyano-1-methylethyl)benzoyl chloride

Product 1

HCID 68419052N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3-(1-cyano-1-methylethyl)benzamideYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a two-layer solution of 5-amino-2-chloro-4-fluorophenol (3.50 g, 21.7 mmol) in tetrahydrofuran (35 mL)/1N aqueous sodium hydrogen carbonate solution (65 mL) was added a solution of 3-(1-cyano-1-methylethyl)benzoyl chloride synthesized above in tetrahydrofuran (30 mL), and the mixture was stirred at room temperature for 4 hr. The aqueous layer was separated, and extracted with ethyl acetate (200 mL). The combined organic layer was washed with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (5.18 g, 72%) as a gray powder.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with ethyl acetate (200 mL)
  3. washThe combined organic layer was washed with water (100 mL) and saturated brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe insoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-454bbcad3d934c5f9f2ceb4cacf8cc3b
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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