Hydrochloric Acid → 2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetic acid

HRID 1930119Notes

Reaction equation

HRID 1930119 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]=[C:22]([Cl:24])[C:21]([CH2:25][C:26]([O:28]C)=[O:27])=[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]=[C:22]([Cl:24])[C:21]([CH2:25][C:26]([OH:28])=[O:27])=[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 59627666Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate2×

Product 1

HCID 498472472-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetic acidYield 55.6%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
55 °C

Procedure

Powdered potassium hydroxide (56.1 mg, 1.00 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate (Intermediate 4-1; 148 mg, 0.33 mmol) in tert-butanol (10 mL) at 55° C. The resulting solution was stirred at 55° C. for 45 minutes, 2M HCl (2 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water (50 mL) and air dried to afford crude product as a pale yellow solid, which contained a minor impurity. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetic acid (79 mg, 55.2%) as a white solid.

Workup

  1. customthe mixture was evaporated
  2. customto remove the organic solvent
  3. filtrationThe suspension was collected by filtration
  4. washwashed with water (50 mL) and air
  5. customdried
  6. customto afford crude product as a pale yellow solid, which
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-5a6e57d6f6524c93907d8dafc17a2356
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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