Potassium Hydroxide → HCID 70664828, compound

HRID 468651Notes

Reaction equation

HRID 468651 reaction equation
[OH-:1].[K+].F[C:4]1[C:5](=[O:30])[N:6]([CH2:17][CH2:18][C@@:19]([CH3:29])([S:25]([CH3:28])(=[O:27])=[O:26])[C:20](OCC)=[O:21])[CH:7]=[C:8]([F:16])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[O:31]1[CH2:35]CCC1.CO.O>>[F:16][C:8]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([O:31][CH3:35])[C:5](=[O:30])[N:6]([CH2:17][CH2:18][C@@:19]([CH3:29])([S:25]([CH3:28])(=[O:27])=[O:26])[C:20]([OH:1])=[O:21])[CH:7]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 21892291Methanol tetrahydrofuran waterHCID 86670655HCID 86670655, compound

Product 1

HCID 70664828HCID 70664828, compoundYield 95%

Conditions

Temperature
50 °C

Procedure

Potassium hydroxide (100 mg, 1.78 mmol) was added to a solution of ethyl (2R)-4-(3,5-difluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (77 mg, 0.19 mmol) in tetrahydrofuran:methanol:water (2:2:1 10 mL). The solution was heated to 50° C. and stirred at this temperature for 4 h. The reaction was concentrated and the residue was dissolved in 1 N aq NaOH (50 mL). The aqueous layer was washed with EtOAc (3×50 mL) and acidified to a pH of 3 using concentrated HCl. The solid was collected via filtration and was washed with water (30 mL) and hexanes (30 mL) to afford the title compound as a white solid (70 mg, 95%). MS (LCMS) m/z 398.0 (M+1). 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.69-1.79 (m, 3H) 2.30-2.46 (m, 1H) 2.55-2.72 (m, 1H) 3.18 (s, 3H) 3.66 (s, 3H) 4.08-4.22 (m, 1H) 4.23-4.38 (m, 1H) 7.39-7.51 (m, 5H) 7.60 (d, 1H).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe residue was dissolved in 1 N aq NaOH (50 mL)
  3. washThe aqueous layer was washed with EtOAc (3×50 mL)
  4. filtrationThe solid was collected via filtration
  5. washwas washed with water (30 mL) and hexanes (30 mL)

Sources & evidence

ORD record
ord-f6274e19800c44df8b905aa46b513d83
Source dataset
uspto-grants-2014_01
Patent number
US08624034B2

Reaction notes

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