Ethyl Acetate → 6-Acetyl-3-fluoro-5,6-dihydro-2-(6-methoxy-3-pyridinyl)-pyrido[3,2-c][1]benzazocine

HRID 2224302Notes

Reaction equation

HRID 2224302 reaction equation
[C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[N:16]=[C:17](Cl)[C:18]([F:20])=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1.CCOC(C)=O>C1(C)C=CC=CC=1.CCO.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.O>[C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[N:16]=[C:17]([C:33]3[CH:32]=[N:31][C:30]([O:29][CH3:28])=[CH:35][CH:34]=3)[C:18]([F:20])=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 162177142-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 743934126-Acetyl-2-chloro-3-fluoro-5,6-dihydro-pyrido[3,2-c][1]benzazocine

Product 1

HCID 692911976-Acetyl-3-fluoro-5,6-dihydro-2-(6-methoxy-3-pyridinyl)-pyrido[3,2-c][1]benzazocineYield 96%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1D (20 mg, 0.066 mmol) in toluene (0.5 mL) and EtOH (0.3 mL) was added a 2M aqueous solution of Na2CO3 (0.3 mL, 0.6 mmol). The resulting solution was purged with argon for 30 minutes and 2A (23.3 mg, 0.099 mmol) was added, followed by a catalytic amount of Pd(PPh3)4. The reaction was heated to 100° C. for 15 minutes, then cooled to ambient temperature. EtOAc and H2O were added, the layers were separated and the organic phase was washed with saturated aqueous NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (SiO2, 100% CH2Cl2 then 100% EtOAc) to afford 2B (23.7 mg, 96%). HPLC Rt=3.182 min; LCMS Found: (M+H)+=376.

Workup

  1. customThe resulting solution was purged with argon for 30 minutes
  2. temperaturecooled to ambient temperature
  3. customthe layers were separated
  4. washthe organic phase was washed with saturated aqueous NaHCO3 solution
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (SiO2, 100% CH2Cl2

Sources & evidence

ORD record
ord-41e76cc03ecd4a4db7980f61858427bb
Source dataset
uspto-grants-2008_05
Patent number
US07378426B2

Reaction notes

Loading…