Water → 6-Acetyl-2-chloro-3-fluoro-5,6-dihydro-pyrido[3,2-c][1]benzazocine

HRID 2224300Notes

Reaction equation

HRID 2224300 reaction equation
Cl[C:2]1[C:7]([CH2:8][N:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH:19]=[CH2:20])[C:10](=[O:12])[CH3:11])=[CH:6][C:5]([F:21])=[C:4]([Cl:22])[N:3]=1.CCN(CC)CC.O>CN(C=O)C.Cl[Pd]Cl>[C:10]([N:9]1[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH:19]=[CH:20][C:2]2[N:3]=[C:4]([Cl:22])[C:5]([F:21])=[CH:6][C:7]=2[CH2:8]1)(=[O:12])[CH3:11]

Participants

6

Reactant 3

HCID 962WaterHCID 8471TriethylamineHCID 59717570N-(2,6-dichloro-5-fluoro-pyridin-3-ylmethyl)-N-(2-vinyl-phenyl)-acetamide

Product 1

HCID 743934126-Acetyl-2-chloro-3-fluoro-5,6-dihydro-pyrido[3,2-c][1]benzazocineYield 21.4%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 1C (0.63 g, 1.85 mmol) and Et3N (0.78 mL, 5.55 mmol) in DMF (15 mL) was added PdCl2 (49 mg, 0.28 mmol) and the reaction was heated to 120° C. When the reaction was complete by HPLC, the mixture was poured into H2O and extracted with Et2O. The Et2O layer was washed with H2O (2×20 mL) and brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue obtained was purified by flash chromatography (SiO2, 100% CH2Cl2 to 10% EtOAc/CH2Cl2) to give 1D (0.12 g, 21%). HPLC Rt=2.77 min. (Column: YMC ODS-A 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA); LCMS Found: (M+H)+=303.

Workup

  1. extractionextracted with Et2O
  2. washThe Et2O layer was washed with H2O (2×20 mL) and brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by flash chromatography (SiO2, 100% CH2Cl2 to 10% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-0f1d01e9c6cf41bca26121e4ca4a95c1
Source dataset
uspto-grants-2008_05
Patent number
US07378426B2

Reaction notes

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