Hydrochloric Acid → Racemic 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoic acid

HRID 1930137Notes

Reaction equation

HRID 1930137 reaction equation
[OH-].[K+].[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH:24]([CH3:29])[C:25]([O:27]C)=[O:26])=[CH:20][C:19]=3[Cl:30])=[CH:14][CH:13]=2)[C:9]([CH3:31])=[N:8][C:7]=1[CH3:32])(=[O:5])[NH2:4].Cl>C(O)(C)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH:24]([CH3:29])[C:25]([OH:27])=[O:26])=[CH:20][C:19]=3[Cl:30])=[CH:16][CH:17]=2)[C:9]([CH3:31])=[N:8][C:7]=1[CH3:32])(=[O:5])[NH2:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 67285935Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoate2×

Product 1

HCID 67285162Racemic 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoic acidYield 74.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Powdered potassium hydroxide (331 mg, 5.90 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoate (Intermediate 8-1; 834 mg, 1.97 mmol) in tert-butanol (20 mL) at 45° C. The resulting solution was stirred at 45° C. for 30 minutes. 2M HCl (6 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water and dried under vacuum to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Fractions containing the desired compound were evaporated to dryness to afford racemic 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoic acid (603 mg, 74.8%) as a white solid. This was purified by preparative chiral-HPLC on a OJ column, eluting isocratically with 30% EtOH in isohexane (acidified with AcOH) as eluent. The fractions containing the desired compound were evaporated to dryness to afford:

Workup

  1. customthe mixture was evaporated
  2. customto remove the organic solvent
  3. filtrationThe suspension was collected by filtration
  4. washwashed with water
  5. customdried under vacuum
  6. customto afford crude product
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b0f57174937741a9829e9ad3ffd18c61
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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