Carvacrol → 6-Chloro-4-isopropoxy-3-(5-isopropyl-2-methyl-phenoxymethyl)-2-methyl-pyridine

HRID 1392681

반응식

HRID 1392681 반응식
[H-].[H-].[H-].[H-].[Li+].[Al+3].C(O[C:11](=O)[C:12]1[C:17]([O:18][CH:19]([CH3:21])[CH3:20])=[CH:16][C:15]([Cl:22])=[N:14][C:13]=1[CH3:23])(C)C.O=S(Cl)Cl.C([O-])([O-])=O.[Cs+].[Cs+].[CH:35]1[C:42]([CH:43]([CH3:45])[CH3:44])=[CH:41][CH:40]=[C:38]([CH3:39])[C:36]=1[OH:37]>C1COCC1.C(Cl)Cl.O>[Cl:22][C:15]1[N:14]=[C:13]([CH3:23])[C:12]([CH2:11][O:37][C:36]2[CH:35]=[C:42]([CH:43]([CH3:45])[CH3:44])[CH:41]=[CH:40][C:38]=2[CH3:39])=[C:17]([O:18][CH:19]([CH3:21])[CH3:20])[CH:16]=1

참가 물질

9

반응물 5

HCID 10364CarvacrolHCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 21226445Aluminium lithium hydrideHCID 865939896-Chloro-4-isopropoxy-2-methyl-nicotinic acid isopropyl ester

생성물 1

HCID 865939916-Chloro-4-isopropoxy-3-(5-isopropyl-2-methyl-phenoxymethyl)-2-methyl-pyridine

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

LiAlH4 (14 mL of 1 M solution in THF, 14 mmol) is added to a solution of 6-chloro-4-isopropoxy-2-methyl-nicotinic acid isopropyl ester (2.0 g, 7.4 mmol) in THF (10 mL) at 0° C. The mixture is stirred for 3 hours at ambient temperature. After quenching with water, the mixture is extracted with EtOAc. The combined extracts are washed with saturated brine, dried (Na2SO4), and concentrated to give the crude alcohol as a colorless oil which is dissolved in CH2Cl2 (10 mL) and treated with SOCl2 (2.7 mL, 37 mmol). The mixture is stirred for 1 hour at room temperature and concentrated in vacuo. The residue is dissolved in DMF (15 mL). To this is added Cs2CO3 (7.2 g, 11 mmol) and carvacrol (1.6 g, 11 mmol). The mixture is stirred for 16 hours at room temperature, poured into water, and extracted with Et2O. The combined extracts are washed with saturated brine, dried (Na2SO4), and concentrated in vacuo. The residue is purified by flash chromatography (elution with Hex/EtOAc 6:1) to yield 6-chloro-4-isopropoxy-3-(5-isopropyl-2-methyl-phenoxymethyl)-2-methyl-pyridine. 1H NMR (CDCl3) 7.05 (d, 1H), 6.82 (s, 1H), 6.79 (d, 1H), 6.724 (s, 1H), 5.02 (s, 2H), 4.60 (m, 1H), 2.88 (m, 1H), 2.59 (s, 3H), 2.12 (s, 3H), 1.37 (d, 6H), 1.24 (d, 6H).

후처리

  1. customAfter quenching with water
  2. extractionthe mixture is extracted with EtOAc
  3. washThe combined extracts are washed with saturated brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give the crude alcohol as a colorless oil which
  7. stirringThe mixture is stirred for 1 hour at room temperature
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue is dissolved in DMF (15 mL)
  10. stirringThe mixture is stirred for 16 hours at room temperature
  11. extractionextracted with Et2O
  12. washThe combined extracts are washed with saturated brine
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated in vacuo
  15. customThe residue is purified by flash chromatography (elution with Hex/EtOAc 6:1)

출처 및 근거

ORD 기록
ord-c04ffc0e97c046eb9eb0173733c600bf
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07342115B2

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