Hydrochloric Acid → Ethyl 2-[(3-fluoro-2-hydroxy-4-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)hydrazono]propanoate

HRID 1188957Notes

Reaction equation

HRID 1188957 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[C:6]([F:9])[C:5]([O:10][C:11]2[CH:12]=[N:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][CH:16]=2)=[CH:4][CH:3]=1.Cl.[N:22]([O-])=O.[Na+].[OH-].[K+].[CH3:28][CH:29](C(=O)C)[C:30]([O:32][CH2:33][CH3:34])=[O:31]>C(O)C.O>[F:9][C:6]1[C:7]([OH:8])=[C:2]([NH:1][N:22]=[C:29]([CH3:28])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:3]=[CH:4][C:5]=1[O:10][C:11]1[CH:12]=[N:13][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][CH:16]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 582370436-Amino-2-fluoro-3-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenol

Product 1

HCID 76710732Ethyl 2-[(3-fluoro-2-hydroxy-4-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)hydrazono]propanoateYield 85%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×

Procedure

To an ice-cooled and stirred mixture of 6-amino-2-fluoro-3-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenol (4.2 g) and concentrated hydrochloric acid (2.6 mL) in ethanol (40 mL) and water (10 mL) was added portionwise a solution of sodium nitrite (1.16 g) in water (20 mL) at −10° C. After stirred at −10° C. for 10 min, the solution was added dropwise to a cooled solution of potassium hydroxide (85%, 2.8 g) and ethyl 2-methyl-3-oxobutanoate (2.2 mL) in ethanol (25 mL) and water (25 mL) below −5° C. After stirred at −5 to −10° C. for 30 min, the mixture was partitioned between ethyl acetate and aqueous citric acid solution. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residual brown oil was purified by silica gel chromatography (ethyl acetate:hexane=2:1 to 4:1, volume ratio) to give the title compound (4.94 g, 85%) as light brown prisms. MS 412 (MH+).

Workup

  1. stirringAfter stirred at −10° C. for 10 min
  2. stirringAfter stirred at −5 to −10° C. for 30 min
  3. customthe mixture was partitioned between ethyl acetate and aqueous citric acid solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residual brown oil was purified by silica gel chromatography (ethyl acetate:hexane=2:1 to 4:1, volume ratio)

Sources & evidence

ORD record
ord-b812088ee68244959a3dc5cfc82ba9c2
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

Loading…