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

HRID 1455756

Reaktionsgleichung

Reaktionsgleichung von HRID 1455756
[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

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-bf4fa1743b7f4402aa35654e482725dc
Quelldatensatz
uspto-grants-2009_01
Patentnummer
US07482350B2

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