Tetramethyltin → 1-(3-fluorobenzyl)-4-[(4-fluorobenzyl)oxy]-3-methylpyridin-2(1H)-one

HRID 1867025Notes

Reaction equation

HRID 1867025 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][N:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[C:8](I)[C:7]1=[O:22].[Li+].[Cl-].[CH3:28][Sn](C)(C)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][N:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[C:8]([CH3:28])[C:7]1=[O:22]

Participants

5

Reactant 3

HCID 11661TetramethyltinHCID 433294Lithium ChlorideHCID 101515901-(3-fluorobenzyl)-4-[(4-fluorobenzyl)oxy]-3-iodopyridin-2(1H)-one

Product 1

HCID 220500191-(3-fluorobenzyl)-4-[(4-fluorobenzyl)oxy]-3-methylpyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 1-(3-fluorobenzyl)-4-[(4-fluorobenzyl)oxy]-3 iodopyridin-2(1H)-one (0.804 g, 1.7 mmol) in DMF (10 mL) and LiCl (0.25 g, 5.9 mmol) was added tetramethyltin (0.49 mL, 3.54 mmol) followed by bistriphenylphosphine-palladium chloride catalyst (0.124 g, 0.177 mmol). The reaction mixture was heated in an oil bath (85°-90° C.) under nitrogen for 3 hours. The solvent was concentrated and the residue was diluted with ethyl acetate and washed with water. The organic extracts were dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by flash column chromatography (20% ethyl acetate in hexane). The appropriate fractions were concentrated. 1H-NMR (CD3OD, 400 MHz) δ 7.59 (d, 1H, J=7.6 Hz), 7.46 (m, 2H), 7.34 (m, 1H), 7.10 (m, 4H), 6.46 (d, 1H, J=7.6 Hz), 5.17 (s, 2H), 5.15 (s, 2H), 1.99 (s, 3H); ES-HRMS m/z 342.1314 (M+H calculated for C20H18NO2F2 requires 342.1300).

Workup

  1. temperatureThe reaction mixture was heated in an oil bath (85°-90° C.) under nitrogen for 3 hours
  2. concentrationThe solvent was concentrated
  3. additionthe residue was diluted with ethyl acetate
  4. washwashed with water
  5. dry with materialThe organic extracts were dried over anhydrous Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by flash column chromatography (20% ethyl acetate in hexane)
  8. concentrationThe appropriate fractions were concentrated

Sources & evidence

ORD record
ord-55abb8e98a7e4e95909803e08a965274
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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