Phosphorus oxychloride → 4-Chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidine

HRID 2191537Notes

Reaction equation

HRID 2191537 reaction equation
[CH3:1][CH:2]1[C:10]2[C:9](O)=[N:8][CH:7]=[N:6][C:5]=2[CH2:4][O:3]1.O=P(Cl)(Cl)[Cl:14]>C(#N)C>[Cl:14][C:9]1[C:10]2[CH:2]([CH3:1])[O:3][CH2:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178434859HCID 178434859, compound

Product 1

HCID 584973354-Chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidineYield 96.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 5-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-ol (1.2 g, 7.9 mmol) in acetonitrile (50 mL) was added via syringe POCl3 (3.6 g, 23.7 mmol) and the mixture heated to reflux for 3 hours. The mixture was allowed to cool to room temperature and then concentrated. The residue was diluted with EtOAc and quenched by pouring into saturated NaHCO3. The organic layer was separated and the aqueous layer extracted with EtOAc (3×100 mL). The combined organic layers were dried (MgSO4) and concentrated to give 4-chloro-5-methyl-5,7-dihydrofuro[3,4-d]pyrimidine (1.3 g, 96%) as a light brown oil which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 8.89 (s, 1H), 5.46 (q, J=6.4 Hz, 1H), 5.15 (dd, J=14.4, 2.8 Hz, 1H), 5.02 (dd, J=14.4, 2.8 Hz, 1H), 1.62 (d, J=6.4 Hz, 3H).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 3 hours
  3. concentrationconcentrated
  4. additionThe residue was diluted with EtOAc
  5. customquenched
  6. additionby pouring into saturated NaHCO3
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted with EtOAc (3×100 mL)
  9. dry with materialThe combined organic layers were dried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-2dd4b2accbd9456b9a951e28f8603cce
Source dataset
uspto-grants-2012_12
Patent number
US08329701B2

Reaction notes

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