Phosphorus oxychloride → 4-Chloro-2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidine

HRID 1455773Notes

Reaction equation

HRID 1455773 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[N:14]=[C:13](O)[C:12]([CH2:16][O:17][C:18]2[CH:23]=[C:22]([CH:24]([CH3:26])[CH3:25])[CH:21]=[CH:20][C:19]=2[CH3:27])=[C:11]([CH3:28])[N:10]=1.P(Cl)(Cl)([Cl:31])=O>>[Cl:31][C:13]1[C:12]([CH2:16][O:17][C:18]2[CH:23]=[C:22]([CH:24]([CH3:25])[CH3:26])[CH:21]=[CH:20][C:19]=2[CH3:27])=[C:11]([CH3:28])[N:10]=[C:9]([C:3]2[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[N:14]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178424918HCID 178424918, compound

Product 1

HCID 575314014-Chloro-2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidine

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(2,6-dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-ol (760 mg, 2.0 mmol) and phosphorous oxychloride (5 mL) is heated at 80° C. under nitrogen with magnetic stirring for 2 h (until starting material is consumed as determined by LC/MS analysis). The reaction mixture is evaporated at reduced pressure, diluted with DCM (50 mL), extracted with sat. NaHCO3 (20 mL×3), dried over anhydrous sodium sulfate, filtered and evaporated to obtain a pale yellow oil. Purification by chromatography on silica gel (10-40% EtOAc/Hexanes) provides the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.08-7.25 (m, 4H), 6.88 (s, 1H), 6.82 (d, J=9 Hz, 1H), 5.28 (s, 2H), 2.91 (m, 1H), 2.74 (s, 3H), 2.21 (s, 3H), 2.14 (s, 6H), 1.28 (d, J=6.8 Hz, 6H); LC-MS found 395.4 (MH+), rt=3.33 min, Method 3.

Workup

  1. custom(until starting material is consumed as determined by LC/MS analysis)
  2. customThe reaction mixture is evaporated at reduced pressure
  3. additiondiluted with DCM (50 mL)
  4. extractionextracted with sat. NaHCO3 (20 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto obtain a pale yellow oil
  9. customPurification by chromatography on silica gel (10-40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-de3ba86da8e342bba39a5a0dc9f34ff0
Source dataset
uspto-grants-2009_01
Patent number
US07482350B2

Reaction notes

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