Hydrochloric Acid → HCID 86652840, compound

HRID 1188904Notes

Reaction equation

HRID 1188904 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[N:11][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[CH:4][C:3]=1[OH:19].Cl.[N:21]([O-])=O.[Na+].[CH3:25][CH:26](C(=O)C)[C:27]([O:29][CH2:30][CH3:31])=[O:28].[OH-].[K+]>C(O)C.O>[OH:19][C:3]1[CH:4]=[C:5]([O:8][C:9]2[CH:10]=[N: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:26]([CH3:25])[C:27]([O:29][CH2:30][CH3:31])=[O:28]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 701Ethyl 2-methylacetoacetateHCID 14797Potassium HydroxideHCID 23668193Sodium NitriteHCID 67118481HCID 67118481, compound

Product 1

HCID 86652840HCID 86652840, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a stirring suspension of 2-amino-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenol (17.28 g) in ethanol (150 mL) was added concentrated hydrochloric acid (13.6 mL) at 0° C. After cooling to −5° C., a solution of sodium nitrite (5.1 g) in water (20 mL) was added dropwise to the mixture with keeping the temperature below −5° C. The mixture was stirred at −10° C. for 20 min. The mixture was added to a mixture of ethyl 2-methyl-3-oxobutanoate (9.8 mL), potassium hydroxide (85%, 14.2 g), ethanol (150 mL) and water (150 mL) at −30 to −25° C. After stirring at −30° C. for 30 min, 1M hydrochloric acid (110 mL) was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residual solid was washed with diethyl ether to give the title compound (21.1 g, 87%) as a brownish-yellow solid. MS 394 (MH+).

Workup

  1. customthe temperature below −5° C
  2. stirringAfter stirring at −30° C. for 30 min
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washThe residual solid was washed with diethyl ether

Sources & evidence

ORD record
ord-280e5298909440b0896eb0b4c6d0a2a9
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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