Phosphorus oxychloride → 4-Chloro-2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidine

HRID 1010861Notes

Reaction equation

HRID 1010861 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C:8]2[N:9]=[C:10](O)[C:11]3[O:16][CH2:15][CH2:14][C:12]=3[N:13]=2)[CH:7]=1.C([O-])(O)=O.[Na+].O=P(Cl)(Cl)[Cl:26]>C(Cl)Cl>[Cl:26][C:10]1[C:11]2[O:16][CH2:15][CH2:14][C:12]=2[N:13]=[C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[F:18])[N:9]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178517511HCID 178517511, compound

Product 1

HCID 211043394-Chloro-2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidineYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ol (100 mg, 0.36 mmol, 1 eq) in POCl3 (5 ml) was stirred under reflux for 1 h. The solution cooled to r.t. and concentrated under reduced pressure to give a white solid which was dissolved in methylene chloride. The solution was cooled to 0° C. and ice was added followed by sat. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and evaporated in vacuo to provide a crude white solid which was purified by flash column chromatography (1:9 EtOAc:Hexane) to afford 4-chloro-2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidine (78 mg, 73%) as a white solid.

Workup

  1. temperatureunder reflux for 1 h
  2. concentrationconcentrated under reduced pressure
  3. customto give a white solid which
  4. temperatureThe solution was cooled to 0° C.
  5. additionice was added
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto provide a crude white solid which
  12. customwas purified by flash column chromatography (1:9 EtOAc:Hexane)

Sources & evidence

ORD record
ord-347d2cffa3ca4424a60d2b4faa2c0e5d
Source dataset
uspto-grants-2011_07
Patent number
US07977342B2

Reaction notes

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