Hydrochloric Acid → HCID 76710731, compound

HRID 1188948Notes

Reaction equation

HRID 1188948 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[OH:19].Cl.[N:21]([O-])=O.[Na+].[OH-].[K+].[CH3:27][CH:28](C(=O)C)[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C(O)C.C(#N)C.O>[OH:19][C:3]1[CH:4]=[C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][CH:14]=2)[CH:6]=[CH:7][C:2]=1[NH:1][N:21]=[C:28]([CH3:27])[C:29]([O:31][CH2:32][CH3:33])=[O:30]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 66886149HCID 66886149, compound

Product 1

HCID 76710731HCID 76710731, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Procedure

To an ice-cooled and stirred mixture of 2-amino-5-[4-(methylsulfonyl)phenoxy]phenol (4.3 g) and concentrated hydrochloric acid (2.8 mL) in ethanol (40 mL) and acetonitrile (10 ml) was added a solution of sodium nitrite (1.27 g) in water (5 mL) at −5 to −10° C., and the mixture was diluted with water (20 mL). After stirred at −5 to −10° C. for 30 min, the resulting clear brown solution was added dropwise to a cooled solution of potassium hydroxide (85%, 3.05 g) and ethyl 2-methyl-3-oxobutanoate (2.44 mL) in ethanol (30 mL) and water (30 ml) at −10 to −20° C. After stirred at −10 to −20° C. for 20 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 light brown solid was washed with ethyl acetate-hexane to give the title compound (5.81 g, 96%) as a light orange solid. MS 391 (MH+).

Workup

  1. stirringAfter stirred at −5 to −10° C. for 30 min
  2. stirringAfter stirred at −10 to −20° C. for 20 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. washThe residual light brown solid was washed with ethyl acetate-hexane

Sources & evidence

ORD record
ord-c556c555b60c4df68866f65e0b8ee1dd
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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