Water → 1-(1-((6-Cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid

HRID 2272537Notes

Reaction equation

HRID 2272537 reaction equation
[OH-].[Na+].Cl.[CH:4]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)=[C:11]([F:20])[C:10]([O:21][CH:22]([CH3:24])[CH3:23])=[C:9]([CH2:25][N:26]3[CH2:31][CH2:30][CH:29]([N:32]4[CH:37]=[CH:36][C:35]([C:38]([O:40]C)=[O:39])=[C:34]([CH3:42])[C:33]4=[O:43])[CH2:28][CH2:27]3)[CH:8]=2)[CH2:6][CH2:5]1.O>CO>[CH:4]1([C:7]2[C:12]([C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)=[C:11]([F:20])[C:10]([O:21][CH:22]([CH3:24])[CH3:23])=[C:9]([CH2:25][N:26]3[CH2:27][CH2:28][CH:29]([N:32]4[CH:37]=[CH:36][C:35]([C:38]([OH:40])=[O:39])=[C:34]([CH3:42])[C:33]4=[O:43])[CH2:30][CH2:31]3)[CH:8]=2)[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 118037731Methyl 1-(1-((6-cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate hydrochloride

Product 1

HCID 917546701-(1-((6-Cyclopropyl-2,4'-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acidYield 99.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2M aqueous sodium hydroxide solution (690 mL) was added to a solution of methyl 1-(1-((6-cyclopropyl-2,4′-difluoro-3-isopropoxybiphenyl-4-yl)methyl)piperidin-4-yl)-3-methyl-2-oxo-1,2-dihydropyridine-4-carboxylate hydrochloride (270 g) in methanol (1.35 L) at room temperature. The mixture was stirred at 50 C for 2 hours and cooled to room temperature. Water (2.70 L) was added to the reaction mixture. The mixture was concentrated in vacuo to remove methanol and neutralized with 2M hydrochloric acid (460 mL) at room temperature. Crystalline seeds were added to the mixture. The mixture was stirred at room temperature for 17 hours. The precipitate was collected by filtration, washed with water (7.00 L) and dried in vacuo at 65 C for 24 hours to give the title compound (245.3 g).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto remove methanol
  3. customat room temperature
  4. additionCrystalline seeds were added to the mixture
  5. stirringThe mixture was stirred at room temperature for 17 hours
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with water (7.00 L)
  8. customdried in vacuo at 65 C for 24 hours

Sources & evidence

ORD record
ord-049c3bd534d84ec298bb74d04f213b0c
Source dataset
uspto-grants-2015_09
Patent number
US09120777B2

Reaction notes

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