Phosphorus oxychloride → HCID 11438401, compound

HRID 1835290Notes

Reaction equation

HRID 1835290 reaction equation
O=P(Cl)(Cl)[Cl:3].[CH3:6][C:7]1[CH2:12][C:11](=O)[CH:10]=[C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)[N:8]=1.N12CCCN=C1CCCCC2>C(Cl)Cl>[Cl:3][C:11]1[CH:12]=[C:7]([CH3:6])[N:8]=[C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)[CH:10]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 68524775HCID 68524775, compound

Product 1

HCID 11438401HCID 11438401, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flask containing 20 ml of POCl3 at 120° C. oil bath was carefully added a solution of 5 g (17 mmol) crude compound 4 and 2.6 ml of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (17 mmol) in 20 ml of methylene chloride. After the addition, the reaction mixture was refluxed for one hour. The resulting mixture was concentrated to dryness and diluted with ethyl acetate. Saturated aqueous NaHCO3 was carefully added to the solution to adjust pH to 5-6. The organic phase was separated and the aqueous phase was extracted with the same volume of EtOAc. The combined organic phases were then washed with brine and dried with magnisium sulfate, filtered and concentrated to dryness. The residue was purified with flash chromatography (silica gel, 5% EtOAc/hexane) to get 1.8 g of compound 5 and 850 mg of a mixture of compound 5 and unreacted compound 3. 1H NMR (CDCl3): δ 7.93 (d, 2H, J=6.7 Hz), 7.48 (d, 1H, J=1.36 Hz), 7.09 (d, 1H, J=1.5 Hz), 7.00 (m, 6H), 2.59 (s, 3H). MS: 314.1

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was refluxed for one hour
  3. concentrationThe resulting mixture was concentrated to dryness
  4. additiondiluted with ethyl acetate
  5. additionSaturated aqueous NaHCO3 was carefully added to the solution
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with the same volume of EtOAc
  8. washThe combined organic phases were then washed with brine
  9. dry with materialdried with magnisium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified with flash chromatography (silica gel, 5% EtOAc/hexane)

Sources & evidence

ORD record
ord-139db8fb101a401fb539da82d4b6e680
Source dataset
uspto-grants-2004_08
Patent number
US06770661B2

Reaction notes

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