2-Bromopyridine → HCID 57425669, compound

HRID 1360114Notes

Reaction equation

HRID 1360114 reaction equation
CON(C)[C:4](=[O:18])[CH:5]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1.C([Li])(C)(C)C>C1COCC1>[N:12]1([CH:5]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[O:18])[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 57425668HCID 57425668, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 57425669HCID 57425669, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

N-Methoxy-N-methyl-2-morpholin-4-yl-2-phenylacetamide (215 mg, 0.813 mmol) was dissolved in 10 mL of dry THF and cooled to −78° C. In a separate flask, 2-bromopyridine (97 μL, 1.0 mmol) was dissolved in 5 mL of dry THF and cooled to −78° C., to which was added tert-Butyl lithium (1.20 mL, 1.7M solution in pentane, 2.0 mmol) dropwise. After stirring for 30 minutes, the mixture transferred to the amide flask dropwise and stirred for approximately one hour. The mixture was quenched with NaHCO3(sat), warmed to ambient temperature and poured into water. The aqueous layer was extracted 3× with EtOAc and the combined organic extracts were dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100/0/0 to 9/1/0.1 CH2Cl2/MeOH/NH4OH), providing partially purified titled product. The residue was further purified by preparative reverse phase HPLC. The appropriate fractions were poured into NaHCO3(aq sat) and extracted twice with EtOAc. The combined organic extracts were dried with Na2SO4, filtered and concentrated in vacuo to provide 2-morpholin-4-yl-2-phenyl-1-pyridin-2-ylethanone. ESI+MS: 283.1 [M+H]+.

Workup

  1. temperaturecooled to −78° C., to which
  2. stirringstirred for approximately one hour
  3. customThe mixture was quenched with NaHCO3(sat)
  4. temperaturewarmed to ambient temperature
  5. additionpoured into water
  6. extractionThe aqueous layer was extracted 3× with EtOAc
  7. dry with materialthe combined organic extracts were dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel chromatography (100/0/0 to 9/1/0.1 CH2Cl2/MeOH/NH4OH)
  11. customproviding partially
  12. custompurified titled product
  13. customThe residue was further purified by preparative reverse phase HPLC
  14. additionThe appropriate fractions were poured into NaHCO3(aq sat)
  15. extractionextracted twice with EtOAc
  16. dry with materialThe combined organic extracts were dried with Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bf2ef88a1ff44451bfa35a598a413c6f
Source dataset
uspto-grants-2011_02
Patent number
US07879839B2

Reaction notes

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