Water → 2,4-Dichloro-6-(4-methylpent-3-en-1-yl)pyrimidine

HRID 2303266Notes

Reaction equation

HRID 2303266 reaction equation
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[N:15]=[C:14]([Cl:16])[CH:13]=[C:12]([CH3:17])[N:11]=1.[CH3:18][C:19]([CH3:23])=[CH:20][CH2:21]Br.O>C1COCC1.C(OCC)(=O)C>[Cl:9][C:10]1[N:15]=[C:14]([Cl:16])[CH:13]=[C:12]([CH2:17][CH2:21][CH:20]=[C:19]([CH3:23])[CH3:18])[N:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 700922-Butene, 1-bromo-3-methyl-HCID 794712,4-Dichloro-6-methylpyrimidineHCID 2724682Lithium diisopropylamide

Product 1

HCID 224884832,4-Dichloro-6-(4-methylpent-3-en-1-yl)pyrimidineYield 74.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

The above synthesis may be carried out as follows: To a solution of LDA (1.28 g, 12 mmol) in THF (30 mL) at −78° C. was added 2,4-dichloro-6-methylpyrimidine (1.96 g, 12 mmol) in THF (15 mL). After stirring for 15 minutes, 3,3-dimethyallyl bromide (1.79 g, 12 mmol) in THF (5 ml) was added dropwise. After the reaction warmed to ambient temperature, water and ethyl acetate was added. The organic layer was separated, the solvent was removed in vacuo, and the residue was chromatographed (ethyl acetate/hexane, 1/19) to give 2.06 g (74%) of 2,4-dichloro-6-(4-methyl-3-pentenyl)pyrimidine (1H NMR (CDCl3) δ7.15 (s, 1), 5.10 (t, 1), 2.80 (t, 2), 2.45 (m, 2), 1.70 (s, 3), 1.55 (s,3)). To a solution of NalO4 (17 g, 81 mmol) and KMnO4 (251 mg, 1.59 mmol) in water was added K2CO3 (1.29 g, 9.38 mmol) and 2,4-dichloro-6-(4-methyl-3-pentenyl)pyrimidine (2.06 g, 8.9 mmol) in t-butanol. After stirring for 16 hours, the reaction was acidified to pH 3 and extracted with ethyl acetate. The organic layer was extracted with aqueous NaHCO3. The aqueous layer was acidified to pH 3 and extracted with ethyl acetate. The organic layer was dried and the solvent removed in vacuo to give 980 mg of 3-(2,4-dichloropyrimidin-6-yl)propionic acid (the compound of formula (XIX)), 1H NMR (CDCl3) δ7.30 (s, 1), 3.05 (t, 2), 2.90 (t, 2). The acid was coupled to piperonylamine under standard conditions with isobutyl chloroformate and N-methylmorpholine to give the compound of formula (XX). Imidazole was added under standard conditions (1-trimethylsilylimidazole and CsF in DMF at 60° C.) to give N-[(1,3-benzodioxol-5-yl)ethyl]-chloro-2-(1H-imidazol-1-yl)pyrimidine-4-propionamide (the compound of formula (Ihh)); MS: 386 (M+H)+.

Workup

  1. customThe above synthesis
  2. customThe organic layer was separated
  3. customthe solvent was removed in vacuo
  4. customthe residue was chromatographed (ethyl acetate/hexane, 1/19)

Sources & evidence

ORD record
ord-2083955fe6d34aff85574531c51bff2e
Source dataset
uspto-grants-2002_08
Patent number
US06432947B1

Reaction notes

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