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

HRID 1399562ノート

反応式

HRID 1399562 の反応式
[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][C:17]([CH3:20])=[CH:16][CH:15]=2)[N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:32][CH2:33][CH3:34]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:32][CH2:33][CH3:34])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[N:3]=1

参加物

5

反応物 3

HCID 336431-IodopropaneHCID 2733832Lithium HexamethyldisilazideHCID 86665648Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)acetate

生成物 1

HCID 86665647Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate収率 39.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
-78 °C

実験手順

A solution of methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)acetate (2.5 g; 8.60 mmol) in dry DMF (40 mL) was cooled to −78° C. LHMDS (9.46 mL; 9.46 mmol; 1M in THF) was added dropwise and the mixture was stirred at −78° C. for 15 min followed by the dropwise addition of iodopropane (1.260 ml; 12.90 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 (2-10%) in heptane to give 1.131 g (37%) of the title compound as a yellow oil. ESI/APCI(+): 333 (M+H).

後処理

  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 (2-10%) in heptane

出典と根拠

ORDレコード
ord-c394e78177414f3393430c19e4e2b1f5
出典データセット
uspto-grants-2014_12
特許番号
US08906906B2

反応ノート

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