Phosphorus oxychloride → HCID 117739138, compound

HRID 708799Notes

Reaction equation

HRID 708799 reaction equation
[F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[C:5](=O)[NH:4][CH:3]=1.P(Cl)(Cl)([Cl:18])=O>>[Cl:18][C:5]1[C:6]2[C:11](=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=2)[C:2]([F:1])=[CH:3][N:4]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 117739242HCID 117739242, compound

Product 1

HCID 117739138HCID 117739138, compoundYield 104.2%

Conditions

Temperature
115 °C

Procedure

To Intermediate 3E (8.8 g, 36.0 mmol) was added phosphoryl trichloride (59.3 mL, 648 mmol). The suspension was heated at 115° C. for 1.0 h. Solvent was removed under high vacuum. The residue was diluted with EtOAc, washed with sat. sodium bicarbonate, brine and dried over sodium sulfate. After evaporation of solvent, the crude product was dissolved in a small amount of chloroform and charged to a 120 g silica gel cartridge which was eluted with 2% EtOAc in hexanes for 6 min, then a 15 min gradient from 2% to 25% EtOAc in hexanes. The desired fractions were combined and concentrated to give Intermediate 3F (8.5 g, 37.5 mmol, 104% yield) as a slightly yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 9.01 (s, 1H) 8.46-8.56 (m, 2H) 8.34 (s, 1H); 19F NMR (376 MHz, chloroform-d) δ ppm −136.54 (s, 1F); MS (ESI) m/z: (M+H)+ 227.1.

Workup

  1. customSolvent was removed under high vacuum
  2. additionThe residue was diluted with EtOAc
  3. washwashed with sat. sodium bicarbonate, brine
  4. dry with materialdried over sodium sulfate
  5. customAfter evaporation of solvent
  6. dissolutionthe crude product was dissolved in a small amount of chloroform
  7. additioncharged to a 120 g silica gel cartridge which
  8. washwas eluted with 2% EtOAc in hexanes for 6 min
  9. customa 15 min gradient
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9fbe1b50f43c43409729b9825af42ec3
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

Loading…