1-Iodopropane → Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)pentanoate

HRID 1399560Notes

Reaction equation

HRID 1399560 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:31][CH2:32][CH3:33]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:31][CH2:32][CH3:33])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1

Participants

5

Reactant 3

HCID 336431-IodopropaneHCID 2733832Lithium HexamethyldisilazideHCID 86665645Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)acetate

Product 1

HCID 86665646Methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)pentanoateYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of methyl 2-(2-chloro-4-methyl-6-phenylpyrimidin-5-yl)acetate (2.5 g; 9.03 mmol) in dry DMF (45 mL) was cooled to −15° C. LHMDS (10.84 mL; 10.84 mmol; 1M in THF) was added dropwise and the mixture was stirred at −15° C. for 15 min followed by the dropwise addition of iodopropane (1.765 mL; 18.07 mmol). After stirring for 2 h at −15° C. the mixture was allowed to warm up to room temperature. After 1 h the reaction was quenched by adding a saturated solution of ammonium chloride. The mixture was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane to give 0.98 g (25%) of the title compound as a yellow oil. ESI/APCI(+): 319 (M+H).

Workup

  1. stirringAfter stirring for 2 h at −15° C. the mixture
  2. temperatureto warm up to room temperature
  3. customAfter 1 h the reaction was quenched
  4. additionby adding a saturated solution of ammonium chloride
  5. extractionThe mixture was extracted twice with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane

Sources & evidence

ORD record
ord-71be82baf7744c43836a6a38223aade3
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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