Phosphorus oxychloride → (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

HRID 388297Notes

Reaction equation

HRID 388297 reaction equation
[CH3:1][C@H:2]1[C:10]2[C:9](O)=[N:8][CH:7]=[N:6][C:5]=2[CH2:4][CH2:3]1.O=P(Cl)(Cl)[Cl:14]>>[Cl:14][C:9]1[C:10]2[C@H:2]([CH3:1])[CH2:3][CH2:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178461168HCID 178461168, compound

Product 1

HCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineYield 49%

Procedure

A mixture of (R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (5.8 g, 38.62 mmol) in POCl3 (20 mL) was refluxed for 5 minutes. Excess POCl3 was removed under vacuum, and the residue was dissolved in DCM (50 mL). The mixture was then added to saturated NaHCO3 (200 mL). The aqueous phase was extracted with DCM (3×100 mL), and the combined organic phases were dried and concentrated. The residue was purified by silica gel chromatography, eluting with ethyl acetate to give (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (3.18 g, 49%). 1H NMR (CDCl3, 400 MHz) δ 8.81 (s, 1H), 3.47 (m, 1H), 3.20 (m, 1H), 3.05 (m, 1H), 2.41 (m, 1H), 1.86 (m, 3H), 1.47 (m, 3H).

Workup

  1. temperaturewas refluxed for 5 minutes
  2. customExcess POCl3 was removed under vacuum
  3. dissolutionthe residue was dissolved in DCM (50 mL)
  4. additionThe mixture was then added to saturated NaHCO3 (200 mL)
  5. extractionThe aqueous phase was extracted with DCM (3×100 mL)
  6. customthe combined organic phases were dried
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-e76ca2d42d5f494db8fa38e5bfaa8476
Source dataset
uspto-grants-2013_02
Patent number
US08377937B2

Reaction notes

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