Water → Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 84288Notes

Reaction equation

HRID 84288 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:34])=[O:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1I.O>O1CCOCC1.[Pd]>[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:33])=[O:34])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 67249327Ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Product 1

HCID 67248709Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateYield 51.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd EnCat™ (172 mg, 0.067 mmol) was added to a mixture of potassium carbonate (298 mg, 2.16 mmol), phenylboronic acid (132 mg, 1.08 mmol), and ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (288 mg, 0.647 mmol) in 1,4-dioxane:water (10 ml, 4:1) in a 20 ml vial. The vial was sealed and the reaction was heated to 80° C. and allowed to stir overnight at that temperature. The reaction was allowed to cool to RT, filtered and the catalyst was washed with methanol (20 mL) and dichloromethane (20 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography using an Analogix SF15-12g column and an eluant of ethyl acetate in heptane (60-100%) to afford the title compound as a white solid (131 mg, 51.2%). LC-MS m/z 396.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (t, J=7.12 Hz, 3 H) 1.79 (s, 3 H) 2.46-2.67 (m, 2 H) 3.14 (s, 3 H) 3.99-4.16 (m, 1 H) 4.22-4.44 (m, 3 H) 6.24-6.39 (m, 1 H) 7.10-7.22 (m, 1 H) 7.38-7.55 (m, 3 H) 7.54-7.63 (m, 2 H).

Workup

  1. customThe vial was sealed
  2. temperatureto cool to RT
  3. filtrationfiltered
  4. washthe catalyst was washed with methanol (20 mL) and dichloromethane (20 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customthe crude product was purified via flash chromatography

Sources & evidence

ORD record
ord-2ace22c043cb49019af53dc5fcb7dc2f
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

Loading…