Tetrahydrofuran → N-(4-Bromo-2-cyano-5-fluoro-6-hydroxy-3-methylphenyl)-2,2-dimethyl-3-[(phenylmethyl)oxy]propionamide

HRID 17363Notes

Reaction equation

HRID 17363 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:6][C:7]1[C:14]([OH:15])=[C:13]([F:16])[C:12]([Br:17])=[C:11]([CH3:18])[C:8]=1[C:9]#[N:10].[C:19](=[O:22])([O-])O.[Na+]>C(OCC)(=O)C>[Br:17][C:12]1[C:13]([F:16])=[C:14]([OH:15])[C:7]([NH:6][C:19](=[O:22])[C:8]([CH3:11])([CH3:9])[CH2:7][O:1][CH2:5][C:4]2[CH:14]=[CH:13][CH:12]=[CH:2][CH:3]=2)=[C:8]([C:9]#[N:10])[C:11]=1[CH3:18]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 516892Sodium BicarbonateHCID 860975142-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile

Product 1

HCID 86630841N-(4-Bromo-2-cyano-5-fluoro-6-hydroxy-3-methylphenyl)-2,2-dimethyl-3-[(phenylmethyl)oxy]propionamideYield 70%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

After cooling, the reaction liquid was concentrated under reduced pressure, and azeotroped with benzene. A tetrahydrofuran solution (7 ml) of the resulting residue was dropwise added to a tetrahydrofuran solution (63 ml) of 2-amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-75) (3.13 g, 12.77 mmol) and sodium hydrogencarbonate (2.68 g, 31.93 mmol), followed by stirring at room temperature for 19 hours. Ethyl acetate was added to the reaction liquid, followed by washing with water and saturated brine. The organic layer was concentrated under reduced pressure, the resulting residue was dissolved in ethanol (30 ml), aqueous 1 N sodium hydroxide solution (24 ml) was added, followed by stirring at 50° C. for 23 hours. After cooling, the reaction liquid was concentrated under reduced pressure, diluted with ethyl acetate, neutralized with aqueous 1 N hydrochloric acid, washed with saturated brine. The organic layer was concentrated under reduced pressure to obtain the entitled compound (5.82 g, 70%) as a yellow white solid.

Workup

  1. temperatureAfter cooling
  2. customthe reaction liquid
  3. concentrationwas concentrated under reduced pressure
  4. customazeotroped with benzene
  5. washby washing with water and saturated brine
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. dissolutionthe resulting residue was dissolved in ethanol (30 ml)
  8. additionaqueous 1 N sodium hydroxide solution (24 ml) was added
  9. stirringby stirring at 50° C. for 23 hours
  10. temperatureAfter cooling
  11. customthe reaction liquid
  12. concentrationwas concentrated under reduced pressure
  13. additiondiluted with ethyl acetate
  14. washwashed with saturated brine
  15. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-c4781a6778eb4504b6f8f268a4146c7c
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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