Phosphorus oxychloride → HCID 86679023, compound

HRID 2203385Notes

Reaction equation

HRID 2203385 reaction equation
P(Cl)(Cl)(Cl)=O.O=[C:7]([NH:12][CH:13]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)[CH2:14][CH2:15][C:16]([F:22])([F:21])[C:17]([F:20])([F:19])[F:18])[C:8]([O:10][CH3:11])=[O:9]>C(Cl)CCl>[F:21][C:16]([F:22])([C:17]([F:20])([F:19])[F:18])[CH2:15][CH2:14][C:13]1[N:12]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[N:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=12

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 86679024HCID 86679024, compound

Product 1

HCID 86679023HCID 86679023, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
120 °C

Procedure

Phosphoryl chloride (1.428 mL, 15.36 mmol) was added to a stirred solution of the intermediate from Step D (0.6534 g, 1.920 mmol) in dry ClCH2CH2Cl (14.44 mL). The resulting solution was heated at 120° C. overnight. Another 8 eq. POCl3 was added and the reaction was heated at 120° C. for 2 days. The reaction was cooled to room temperature and concentrated in vacuo. The reaction was diluted with water and EtOAc and basified by the careful addition of saturated aq. NaHCO3 until not further effervescence was observed. The layers were separated and the aqueous layer was further extracted with EtOAc (2×). The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by silica gel chromatography using a hexanes/EtOAc gradient to afford the desired product, as a colorless solid. 1H NMR (500 MHz, CHCl3-d) δ 9.31 (d, J=7.2 Hz, 1H); 7.59 (d, J=9.1 Hz, 1H); 7.08 (dd, J=9.0, 6.6 Hz, 1H); 6.96-6.90 (m, 1H); 4.03 (s, 3H); 3.25-3.19 (m, 2H); 2.66-2.52 (m, 2H). m/z=323.0 (M+H).

Workup

  1. temperaturethe reaction was heated at 120° C. for 2 days
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. additionThe reaction was diluted with water and EtOAc
  5. additionbasified by the careful addition of saturated aq. NaHCO3 until not further effervescence
  6. customThe layers were separated
  7. extractionthe aqueous layer was further extracted with EtOAc (2×)
  8. washThe organic layer was washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto give the crude product
  12. customThis was purified by silica gel chromatography

Sources & evidence

ORD record
ord-091ed9f2ab2f45008f589df1c402a29f
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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