Potassium Hydroxide → HCID 49846225, compound

HRID 1930160Notes

Reaction equation

HRID 1930160 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[C:23]([F:24])=[CH:22][C:21]([CH:25]([CH3:30])[C:26]([O:28]C)=[O:27])=[CH:20][C:19]=3[F:31])=[CH:14][CH:13]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]>CC(O)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:23]([F:24])=[CH:22][C:21]([CH:25]([CH3:30])[C:26]([OH:28])=[O:27])=[CH:20][C:19]=3[F:31])=[CH:16][CH:17]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59627653HCID 59627653, compound2×

Product 1

HCID 49846225HCID 49846225, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Potassium hydroxide (0.396 g, 7.05 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)propanoate (Intermediate 21-1; 1 g, 2.35 mmol) in t-BuOH (15.16 mL) at room temperature. The resulting solution was stirred at 45° C. for 5 hours, a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), evaporated to dryness and redissolved in water (10 mL), filtered through nylon, washed with water and dried under vacuum to afford product as a white solid. The 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/MeOH as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)propanoic acid (0.530 g, 54.8%) as a white powder.

Workup

  1. customa precipitate formed
  2. customThe reaction mixture was quenched with 2M HCl (5 mL)
  3. customevaporated to dryness
  4. dissolutionredissolved in water (10 mL)
  5. filtrationfiltered through nylon
  6. washwashed with water
  7. customdried under vacuum
  8. customto afford product as a white solid
  9. customThe product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  10. additionFractions containing the desired compound
  11. customwere evaporated to dryness

Sources & evidence

ORD record
ord-87bd6f69b90c4c559f96a1a29b8722f8
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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