Hydrochloric Acid → 5'-[(2-Chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylic acid

HRID 970218Notes

Reaction equation

HRID 970218 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:24])=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([O:22]C)=[O:21])=[CH:16][CH:15]=2)[CH:13]=1)=[O:6].O.[OH-].[Li+].C1COCC1.Cl>O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][N:27]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:24])=[C:12]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([OH:22])=[O:21])=[CH:18][CH:19]=2)[CH:13]=1)=[O:6]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 21090582Methyl 5'-[(2-chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylate

Product 1

HCID 210905805'-[(2-Chloroisonicotinoyl)amino]-2'-methyl-1,1'-biphenyl-4-carboxylic acidYield 73.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methyl 5′-[(2-chloroisonicotinoyl)amino]-2′-methyl-1,1′-biphenyl-4-carboxylate (1.63 g, 4.28 mmol) and lithium hydroxide monohydrate (376 mg, 9.0 mmol) were mixed in water (5 ml) and THF (10 ml) and stirred at room temperature for 90 h. The pH was adjusted to pH3 by addition of hydrochloric acid (2N) and the mixture extracted with ethyl acetate (3×50 ml). The combined extracts were washed with water (75 ml), brine (75 ml), dried (magnesium sulphate) and concentrated under vacuum. The residue was purified by flash column chromatography on silica eluting with DCM/ethanol/ammonia (30:8:1 then 20:8:1). The solvents were evaporated under vacuum to give 5′-[(2-chloroisonicotinoyl)amino]-2′-methyl-1,1′-biphenyl-4-carboxylic acid (1.15 g, 73%). LCMS: retention time 3.53 min, MH+367.

Workup

  1. extractionthe mixture extracted with ethyl acetate (3×50 ml)
  2. washThe combined extracts were washed with water (75 ml), brine (75 ml)
  3. dry with materialdried (magnesium sulphate)
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash column chromatography on silica eluting with DCM/ethanol/ammonia (30:8:1
  6. customThe solvents were evaporated under vacuum

Sources & evidence

ORD record
ord-03ac7039616a44009fbe2cb005d40054
Source dataset
uspto-grants-2007_12
Patent number
US07309800B2

Reaction notes

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