Triethylamine → HCID 22050193, compound

HRID 1832011Notes

Reaction equation

HRID 1832011 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)[CH3:26]>C(#N)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[C:25]#[CH:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 22050117HCID 22050117, compound

Product 1

HCID 22050193HCID 22050193, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Degassed a solution of 4-(benzyloxy)-1-(3-fluorobenzyl)-3-iodopyridin-2(1H)-one (2.01 g, 4.62 mmol) in anhydrous acetonitrile (25 mL) under argon atmosphere. Triethylamine (1.11 g, 11 mmol) was added and quickly degassed. The reaction mixture was chilled in an ice bath for 15 minutes before adding bistriphenylphosphine-palladium chloride (0.34 g, 0.48 mmol) and cuprous iodide (0.2 g). The reaction was stirred at room temperature for 30 minutes before heating at 60° C. under an atmosphere of argon for 2 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 CH2Cl2 (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 using 30% ethyl acetate in hexane. The appropriate fractions were combined and concentrated under reduced pressure to afford the desired product (1.34 g, 72%) as a light yellow solid. 1H-NMR (CD3OD, 400 MHz) δ 7.74 (d, 1H, J=7.6 Hz), 7.47 (d, 2H, J=7.6 Hz), 7.35 (m, 4H), 7.09 (m, 3H), 6.46 (d, 1H, J=7.6 Hz), 5.26 (s, 2H), 5.13 (s, 2H), 0.18 (s, 9H); ES-HRMS m/z 406.1638 (M+H calculated for C24H25NO2FSi requires 406.1610). Step 3. Preparation of 4-(benzyloxy)-3-ethynyl-1-(3-fluorobenzyl)pyridin-2(1H)-one

Workup

  1. customquickly degassed
  2. temperatureThe reaction mixture was chilled in an ice bath for 15 minutes
  3. temperaturebefore heating at 60° C. under an atmosphere of argon for 2 hours
  4. filtrationThe reaction mixture was filtered through a bed of celite
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionThe dark brown residue was diluted with CH2Cl2 (100 mL)
  7. washwashed with water
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe dark brown residue was purified by flash chromatography
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-af1ce3c62a034c8ea2ccc072c6ded6f2
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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