Methanol → (2R)-4-{5-Fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoic acid

HRID 468646Notes

Reaction equation

HRID 468646 reaction equation
[OH-].[K+].[F:3][C:4]1[C:5]([C:24]2[CH:29]=[CH:28][C:27]([N:30]3[N:34]=[CH:33][CH:32]=[N:31]3)=[CH:26][CH:25]=2)=[CH:6][C:7](=[O:23])[N:8]([CH2:10][CH2:11][C@@:12]([CH3:22])([S:18]([CH3:21])(=[O:20])=[O:19])[C:13]([O:15]CC)=[O:14])[CH:9]=1.CO>CC1CCCO1.O>[F:3][C:4]1[C:5]([C:24]2[CH:25]=[CH:26][C:27]([N:30]3[N:34]=[CH:33][CH:32]=[N:31]3)=[CH:28][CH:29]=2)=[CH:6][C:7](=[O:23])[N:8]([CH2:10][CH2:11][C@@:12]([CH3:22])([S:18]([CH3:21])(=[O:20])=[O:19])[C:13]([OH:15])=[O:14])[CH:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 86670651Ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate

Product 1

HCID 70664611(2R)-4-{5-Fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoic acidYield 96.1%

Reagents, catalysts & solvents 1

HCID 67831299Water methyl tetrahydrofuranSolvent

Procedure

Potassium hydroxide (1.30 g, 23.2 mmol) was added to a solution of ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate (1.54 g, 3.33 mmol) in 2-methyltetrahydrofuran:water (2:1 42.5 mL) and the solution was stirred at rt overnight. Methanol (5 mL) was added and the reaction was heated to 60° C. The reaction mixture was stirred at this temperature for 2 h. The reaction was concentrated and triturated in 3 M aq HCl. The solid was collected via filtration and washed with water (20 mL) and hexanes (20 mL). The solid was dried under vacuum to afford the title compound as a white solid (1.39 g, 96.1%). MS (LCMS) m/z 435.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58 (s, 3H) 2.13-2.30 (m, 0H) 2.41-2.61 (m, 1H) 3.17 (s, 3H) 3.89-4.13 (m, 2H) 6.59 (d, J=7.81 Hz, 1H) 6.56-6.63 (m, 1H) 7.79 (dd, J=8.78, 1.76 Hz, 3H) 8.09 (d, J=6.83 Hz, 1H) 8.12-8.17 (m, 2H) 8.19 (s, 2H).

Workup

  1. temperaturethe reaction was heated to 60° C
  2. stirringThe reaction mixture was stirred at this temperature for 2 h
  3. concentrationThe reaction was concentrated
  4. customtriturated in 3 M aq HCl
  5. filtrationThe solid was collected via filtration
  6. washwashed with water (20 mL) and hexanes (20 mL)
  7. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-c944ed59efa241d0b84fd67aa2bd28c8
Source dataset
uspto-grants-2014_01
Patent number
US08624034B2

Reaction notes

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