Carvacrol → 2,4-Dichloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidine

HRID 1091938

反応式

HRID 1091938 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9]Cl)=[C:4]([CH3:11])[N:3]=1.[CH:12]1[C:19]([CH:20]([CH3:22])[CH3:21])=[CH:18][CH:17]=[C:15]([CH3:16])[C:13]=1[OH:14].CC([O-])(C)C.[K+]>CC(N(C)C)=O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9][O:14][C:13]2[CH:12]=[C:19]([CH:20]([CH3:21])[CH3:22])[CH:18]=[CH:17][C:15]=2[CH3:16])=[C:4]([CH3:11])[N:3]=1

参加物

5

反応物 3

HCID 10364Carvacrol2 回HCID 135682822,4-Dichloro-5-(chloromethyl)-6-methylpyrimidineHCID 23665647Potassium tert-butoxide2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of 2,4-dichloro-5-chloromethyl-6-methyl-pyrimidine (17.4 g, 82.7 mmol) and carvacrol (6.21 g, 41.4 mmol) in DMA (166 mL) at 0° C. under nitrogen with magnetic stirring is added KOtBu (42 mL of 1 M in THF, 42 mmol) in dropwise fashion over 20 min. The resulting redish-orange colored solution is allowed to slowly warm to ambient temperature (˜2 h) and stir for 18 h. The reaction mixture is re-cooled to 0° C. and another portion of carvacrol is added (6.21, 41.4 mmol) followed by dropwise addition of KOtBu (42 mL of 1 M in THF, 42 mmol). The reaction mixture is allowed to slowly warm to ambient temperature (˜2 h) and stir for 18 h. The reaction mixture is partitioned between EtOAc (200 mL) and water (60 mL), the organic layer is separated, washed with water (60 mL×3), brine (60 mL), dried over sodium sulfate, filtered and evaporated at reduced pressure to obtain an orange oil. The crude product is dissolved in hexanes (300 mL), quickly extracted with Claisen's alkali (50 mL×2), dried over sodium sulfate, filtered and evaporated to obtain an orange oil. Purification by chromatography on silica gel (10 EtOAc/Hexanes) provides the title compound as a colorless oil that solidifies on standing. LC/MS (Method 3), M+H=325.2, Rt=3.03 min.; 1H NMR (CDCl3) δ=7.09 (d, 1H), 6.82 (d, 1H), 6.81 (s, 1H), 5.17 (s, 2H), 2.90 (m, 1H), 2.68 (s, 3H), 2.14, (s, 3H), 1.26 (d, 6H).

後処理

  1. temperatureThe reaction mixture is re-cooled to 0° C.
  2. temperatureto slowly warm to ambient temperature (˜2 h)
  3. stirringstir for 18 h
  4. customThe reaction mixture is partitioned between EtOAc (200 mL) and water (60 mL)
  5. customthe organic layer is separated
  6. washwashed with water (60 mL×3), brine (60 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated at reduced pressure
  10. customto obtain an orange oil
  11. extractionquickly extracted with Claisen's alkali (50 mL×2)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customto obtain an orange oil
  16. customPurification by chromatography on silica gel (10 EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-cd23599570f64536b53f50d9fb691342
出典データセット
uspto-grants-2012_03
特許番号
US08129395B2

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