Toluene → 4-[5-(4-Morpholinylcarbonyl)-1,6-dihydro-2-pyridinyl]phenol

HRID 494795Notes

Reaction equation

HRID 494795 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[C:16](=[O:19])([O-])[O-].[Na+].[Na+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:40]1(C)[CH:45]=[CH:44]C=[CH:42][CH:41]=1>C(OCC)(=O)C.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>[N:10]1([C:8]([C:5]2[CH2:6][NH:7][C:2]([C:40]3[CH:45]=[CH:44][C:16]([OH:19])=[CH:42][CH:41]=3)=[CH:3][CH:4]=2)=[O:9])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 8574994-(6-Chloropyridine-3-carbonyl)morpholineHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 222746924-[5-(4-Morpholinylcarbonyl)-1,6-dihydro-2-pyridinyl]phenolYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of Example 44A (4.0 g, 17.6 mmol), Pd(Ph3P)4 (1.0 g, 0.86 mmol), 4-O-tert-butyldimethylsilyl-phenylboric acid (4.9 g, 23.6 mmol) in toluene (60 mL) and aqueous sodium carbonate (2.76 g dissolved in 25 mL water) was heated to reflux for 12 hours, then cooled to ambient temperature. The mixture was diluted with ethyl acetate (100 mL), washed with water (1×50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was stirred in THF (200 mL) containing tetrabutylammonium fluoride (30 mL, 1.0M, 30.0 mmol) for 16 hours. The mixture was diluted with ethyl acetate (100 mL), washed sequentially with water (1×50 mL), aqueous ammonium chloride (1×50 mL), brine (1×50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to give a solid. The solid was precipitated from ethyl acetate (75 mL), filtered to provide the titled compound as a tan solid (4.27 g, 70%).

Workup

  1. temperatureto reflux for 12 hours
  2. washwashed with water (1×50 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. washwashed sequentially with water (1×50 mL), aqueous ammonium chloride (1×50 mL), brine (1×50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a solid
  11. customThe solid was precipitated from ethyl acetate (75 mL)
  12. filtrationfiltered

Sources & evidence

ORD record
ord-5941f025454d417f8869ed2a545f380e
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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