Sodium Methoxide → 2-Chloro-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine

HRID 1091952

Reaction equation

HRID 1091952 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][O:10][C:11]2[CH:16]=[C:15]([CH:17]([CH3:19])[CH3:18])[CH:14]=[CH:13][C:12]=2[CH3:20])=[C:4]([CH3:21])[N:3]=1.[CH3:22][O-:23].[Na+]>CO>[Cl:1][C:2]1[N:7]=[C:6]([O:23][CH3:22])[C:5]([CH2:9][O:10][C:11]2[CH:16]=[C:15]([CH:17]([CH3:19])[CH3:18])[CH:14]=[CH:13][C:12]=2[CH3:20])=[C:4]([CH3:21])[N:3]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 575314422,4-Dichloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidine

Product 1

HCID 575314062-Chloro-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ˜70% 2,4-dichloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidine (2.64 g, ˜5.68 mmol) is cooled to −5° C. under nitrogen with magnetic stirring. A 0.5 M solution of NaOMe in MeOH (11.4 mL) is added in rapid dropwise fashion. After 1 h, reaction is complete based on LC/MS analysis. The reaction mixture is evaporated at reduced pressure, diluted with DCM (15 mL), filtered and evaporated to obtain a pale yellow oil consisting of an isomeric mixture of mono-methoxy adducts. Purification on silica gel (10-60% EtOAc/Hexanes) provides a colorless oil containing the desired isomer (first to elute) plus impurity from the starting material. 1H NMR (400 MHz, CDCl3) δ 7.06 (d, J=8 Hz, 1H), 6.82 (s, 1H), 6.78 (d, J=8 Hz, 1H), 5.05 (s, 2H), 4.04 (s, 3H), 2.80 (m, 1H), 2.55 (s, 3H), 2.13 (s, 3H), 1.26 (d, J=6.8 Hz, 6H); LC-MS found 321.1 (MH+), rt=1.73 min, Method 2.

Workup

  1. customreaction
  2. customThe reaction mixture is evaporated at reduced pressure
  3. additiondiluted with DCM (15 mL)
  4. filtrationfiltered
  5. customevaporated
  6. customto obtain a pale yellow oil
  7. additionconsisting of an isomeric mixture of mono-methoxy adducts
  8. customPurification on silica gel (10-60% EtOAc/Hexanes)
  9. customprovides a colorless oil
  10. additioncontaining the desired
  11. washisomer (first to elute) plus impurity from the starting material
  12. custom321.1 (MH+), rt=1.73 min, Method 2

Sources & evidence

ORD record
ord-34c5febfbfcb4b70ab9c957f0728b8b0
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Linked notes

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