Potassium Phosphate, Tribasic → Ethyl (2R)-4-{5-fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate

HRID 1625022Notes

Reaction equation

HRID 1625022 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:9][S:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.[F:20][C:21]1[C:22](I)=[CH:23][C:24](=[O:40])[N:25]([CH2:27][CH2:28][C@@:29]([CH3:39])([S:35]([CH3:38])(=[O:37])=[O:36])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:26]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[F:20][C:21]1[C:22]([C:14]2[CH:15]=[CH:16][C:11]([S:10][CH3:9])=[CH:12][CH:13]=2)=[CH:23][C:24](=[O:40])[N:25]([CH2:27][CH2:28][C@@:29]([CH3:39])([S:35]([CH3:38])(=[O:36])=[O:37])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:26]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339594-(Methylthio)phenylboronic acidHCID 67249679Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Product 1

HCID 86670638Ethyl (2R)-4-{5-fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoateYield 99%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

1,4-Dioxane (10 ml) and 3 M aq K3PO4 (1.12 mL, 3.3 mmol) was added to a flask containing [4-(methylthio)phenyl]boronic acid (0.283 g, 1.68 mmol), Pd(dppf)Cl2 (82 mg, 0.112 mmol) and ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate, T2, (500 mg, 1.12 mmol) that was previously flushed with nitrogen. The mixture was heated to 60° C. and stirred at this temperature for 1 h. The reaction mixture was diluted with EtOAc and washed with water. The organics were dried (MgSO4), filtered, and concentrated. The crude product was purified via flash chromatography on a 40 g silica column and an eluent of EtOAc in n-heptane (0-100%) to afford the title compound as a gum (492 mg, 99%). MS (LCMS) m/z 442.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d)δ ppm 1.17-1.27 (m, 3 H) 1.74 (s, 3 H) 2.38-2.61 (m, 5 H) 3.09 (s, 3 H) 3.88-4.02 (m, 1 H) 4.17-4.32 (m, 3 H) 6.57 (d, J=7.61 Hz, 1 H) 7.21-7.34 (m, 3 H) 7.37-7.48 (m, 2 H).

Workup

  1. customwas previously flushed with nitrogen
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with water
  4. dry with materialThe organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified via flash chromatography on a 40 g silica column

Sources & evidence

ORD record
ord-5de6acb801694665963bdca061f6bc4c
Source dataset
uspto-grants-2014_07
Patent number
US08779148B2

Reaction notes

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