Dimethylformamide → HCID 57950294, compound

HRID 930741Notes

Reaction equation

HRID 930741 reaction equation
[CH:1]1([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:12]1[CH:17]=[CH:16][N+:15]([O-])=[CH:14][CH:13]=1.CN(C=[O:23])C>CC(OC(C)=O)=O.CO.O>[CH:1]1([CH2:7][O:8][C:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:23])[CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7507CyclohexanemethanolHCID 24758Sodium hydrideHCID 707244-chloropyridine N-oxide

Product 1

HCID 57950294HCID 57950294, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 7918Acetic AnhydrideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of cyclohexylmethanol (1.1 mL, 9.3 mmol) in DMF (8 mL) was added NaH (60% weight dispersion in mineral oil, 0.37 g, 9.3 mmol) in one portion. After the bubbles disappeared, 4-chloropyridine N-oxide (1.0 g, 7.7 mmol) was added. The reaction was stirred at room temperature under Ar until complete. The reaction was quenched with water and the aqueous mixture was extracted with CH2Cl2. The combined organic extracts were washed with H2O and 5% aqueous LiCl and dried over Na2SO4. After filtration and concentration, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give a yellow solid. The yellow solid was suspended in Ac2O (5 mL) and heated at 140° C. for 4 h. The reaction mixture was cooled, diluted with CH3OH/H2O (10 mL, 1:1) and stirred at room temperature for 1 h. The mixture was concentrated, and the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give the title compound (0.92 g, 58%) as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 11.03 (s, 1H), 7.21 (d, J=7.2 Hz, 1H), 5.83 (dd, J=7.2, 2.4 Hz, 1H), 5.64 (d, J=2.4 Hz, 1H), 3.72 (d, J=6.0 Hz, 2H), 1.84-1.68 (m, 6H), 1.30-1.01 (m, 5H).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe aqueous mixture was extracted with CH2Cl2
  3. washThe combined organic extracts were washed with H2O and 5% aqueous LiCl
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)
  7. customto give a yellow solid
  8. temperatureheated at 140° C. for 4 h
  9. temperatureThe reaction mixture was cooled
  10. stirringstirred at room temperature for 1 h
  11. concentrationThe mixture was concentrated
  12. customthe residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-67ca308a37c6489094009a05f624a7ba
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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