Phosphorus oxychloride → 4-Chloro-6-(methoxymethyl)pyrimidine

HRID 1875909Notes

Reaction equation

HRID 1875909 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6](O)[CH:5]=1.P(Cl)(Cl)([Cl:13])=O>ClCCl>[Cl:13][C:6]1[CH:5]=[C:4]([CH2:3][O:2][CH3:1])[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178494553HCID 178494553, compound

Product 1

HCID 143061714-Chloro-6-(methoxymethyl)pyrimidineYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-(Methoxymethyl)pyrimidin-4-ol (1.38 g, 9.85 mmol) was taken up in dichloromethane (14 ml) and phosphorous oxychloride (9 mL, 97 mmol) was added at ambient temperature. The mixture was stirred at ambient for 18 h and concentrated. The residue was taken up in ice-water and the pH was adjusted to 7 with 1N sodium hydroxide. The mixture was extracted with chloroform and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (5-10% ethyl acetate/chloroform) to afford 4-chloro-6-(methoxymethyl)pyrimidine (1.2 g, 7.57 mmol, 77% yield) as a pale yellow oil, which solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 8.88 (1H, d, J=1.01 Hz), 7.52 (1H, d, J=1.01 Hz), 4.53 (2H, s), 3.50 (3H, s). MS (LC/MS) R.T.=0.98; [M+H]+=159.10.

Workup

  1. concentrationconcentrated
  2. extractionThe mixture was extracted with chloroform
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (5-10% ethyl acetate/chloroform)

Sources & evidence

ORD record
ord-8a849a0446214321acd539df98d0135e
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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