Triethylamine → 4-(benzyloxy)-1-(3-fluorobenzyl)-3-methylpyridin-2(1H)-one

HRID 1832015Notes

Reaction equation

HRID 1832015 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:11](=[O:23])[C:10]=1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25](N(CC)CC)C.C[Sn](C)(C)C>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:11](=[O:23])[C:10]=1[CH3:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11661TetramethyltinHCID 22050117HCID 22050117, compound

Product 1

HCID 220499144-(benzyloxy)-1-(3-fluorobenzyl)-3-methylpyridin-2(1H)-oneYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 4-(benzyloxy)-1-(3-fluorobenzyl)-3-iodopyridin-2(1H)-one (1.03 g, 2.36 mmol) in anhydrous DMF (15 mL) under argon atmosphere was added triethylamine (1.11 g, 11 mmol). The reaction mixture was chilled in an ice bath for 15 minutes before adding tetramethyl tin (2.10 g, 11.75 mmol) followed by bistriphenylphosphine-palladium chloride (0.166 g, 0.24 mmol). The reaction was stirred at room temperature for 30 minutes before heating at 950 C under an atmosphere of argon for 3 hours. The reaction mixture was filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The dark brown residue was diluted with ethyl acetate (100 mL) and washed with water. The organic extracts were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The dark brown residue was purified by flash chromatography (30% ethyl acetate in hexane). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (0.1758 g, 22%) as a light yellow solid. The product was further purified by reverse phase HPLC using a 10-90% acetonitrile/water (30 minute gradient) at a 100 mL/min flow rate, to afford a cleaner product as a light yellow solid (0.0975 g, 8%). 1H-NMR (CD3OD, 400 MHz) δ 7.58 (d, 1H, J=7.6 Hz)), 7.35 (m, 6H), 6.98 (m, 3H), 6.46 (d, 1H, J=7.6 Hz), 5.19 (s, 2H), 5.15 (s, 2H), 2.0 (s, 3H); ES-HRMS m/z 324.1366 (M+H calculated for C20H19NO2F requires 324.1394).

Workup

  1. temperatureThe reaction mixture was chilled in an ice bath for 15 minutes
  2. temperaturebefore heating at 950 C under an atmosphere of argon for 3 hours
  3. filtrationThe reaction mixture was filtered through a bed of celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionThe dark brown residue was diluted with ethyl acetate (100 mL)
  6. washwashed with water
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe dark brown residue was purified by flash chromatography (30% ethyl acetate in hexane)
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d44708ddfdba4f50ae16ee492c148d7a
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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