Phenylacetylene → 1(2H)-Pyridinebutanoic acid, 5-fluoro-α-methyl-α-(methylsulfonyl)-2-oxo-4-(2-phenylethynyl)-, ethyl ester, (αR)-

HRID 468655Notes

Reaction equation

HRID 468655 reaction equation
[F:1][C:2]1[C:3](I)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1.C(N(C(C)C)CC)(C)C.[C:32]1([C:38]#[CH:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[F:1][C:2]1[C:3]([C:39]#[C:38][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1

Participants

8

Reactant 3

HCID 10821PhenylacetyleneHCID 81531DiisopropylethylamineHCID 67249679Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Product 1

HCID 866706621(2H)-Pyridinebutanoic acid, 5-fluoro-α-methyl-α-(methylsulfonyl)-2-oxo-4-(2-phenylethynyl)-, ethyl ester, (αR)-Yield 82.8%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (500 mg, 1.12 mmol) and diisopropylethylamine (6.0 mL, 30 mmol) in tetrahydrofuran (15 mL) was degassed with nitrogen. Pd(PPh3)4 (65.4 mg, 0.056) and copper iodide (21.8 mg, 0.112 mmol) were added to the solution, followed by phenylacetylene (150 uL, 1.4 mmol). The reaction was allowed to stir until complete via TLC. The reaction was diluted with EtOAc (100 mL) and washed with saturated aq NH4Cl (100 mL) and brine (100 mL), dried (MgSO4), filtered, and concentrated. The crude residue was purified via flash chromatography using a Varian SF15-24 g column and an eluent of EtOAc in hexanes (30-80%) to afford the title compound as a yellow solid (389 mg, 82.6%). MS (LCMS) m/z 420.0 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (t, 3H) 1.75 (s, 3H) 2.42-2.61 (m, 2H) 3.11 (s, 3H) 3.91-4.00 (m, 1H) 4.19-4.27 (m, 1H) 4.30 (q, J=7.02 Hz, 2H) 6.72 (d, J=6.63 Hz, 1H) 7.27 (t, J=2.34 Hz, 2H) 7.35-7.44 (m, 2H) 7.55-7.60 (m, 2H).

Workup

  1. washwashed with saturated aq NH4Cl (100 mL) and brine (100 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified via flash chromatography

Sources & evidence

ORD record
ord-1d16e9a7d29b499ba6bddb093f3e5bd5
Source dataset
uspto-grants-2014_01
Patent number
US08624034B2

Reaction notes

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