1,2-Dichloroethane → 4,6-Dichloro-5-cyclopropylpyrimidine

HRID 1192396Notes

Reaction equation

HRID 1192396 reaction equation
C1(C2C(O)=[N:6][CH:7]=[N:8][C:9]=2O)CC1.O=P(Cl)(Cl)[Cl:14].CCN([CH:23]([CH3:25])[CH3:24])C(C)C.Cl[CH2:27][CH2:28][Cl:29]>>[Cl:29][C:28]1[C:27]([CH:23]2[CH2:25][CH2:24]2)=[C:9]([Cl:14])[N:8]=[CH:7][N:6]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 178518200HCID 178518200, compound

Product 1

HCID 544142814,6-Dichloro-5-cyclopropylpyrimidineYield 78%

Procedure

To a stirred solution of 5-cyclopropyl-pyrimidine-4,6-diol (1.35 g, 8.87 mmol) in DCE (35 mL) was added slowly POCl3 (4.14 mL, 44.4 mmol) followed by DIEA (1.72 g, 13.3 mmol). The reaction mixture was heated to reflux for 2 days. After cooling, the solvent was evaporated in vacuo. The residue was partitioned between 5% NaHCO3 and EtOAc. The organic phase was washed with brine, dried, and passed through a Silica gel pad to give 4,6-dichloro-5-cyclopropyl-pyrimidine (1.30 g, 78%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ (s, 1H), 1.65 (m, 1H), 1.03 (m, 2H), 1.58 (m, 2H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 days
  3. temperatureAfter cooling
  4. customthe solvent was evaporated in vacuo
  5. customThe residue was partitioned between 5% NaHCO3 and EtOAc
  6. washThe organic phase was washed with brine
  7. customdried

Sources & evidence

ORD record
ord-76014387f6fd4d48b545c6f4db0ae5fc
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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