Iodine → 5-Chloro-4-(dimethoxymethyl)-2-(3-methoxypropyl)pyridine

HRID 2428091ノート

反応式

HRID 2428091 の反応式
II.Br[CH2:4][CH2:5][CH2:6][O:7][CH3:8].Br[C:10]1[CH:15]=[C:14]([CH:16]([O:19][CH3:20])[O:17][CH3:18])[C:13]([Cl:21])=[CH:12][N:11]=1.CCOC(C)=O>C1COCC1.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:21][C:13]1[C:14]([CH:16]([O:19][CH3:20])[O:17][CH3:18])=[CH:15][C:10]([CH2:4][CH2:5][CH2:6][O:7][CH3:8])=[N:11][CH:12]=1

参加物

7

反応物 4

HCID 807IodineHCID 8857Ethyl AcetateHCID 5245511-Bromo-3-methoxypropane2 回HCID 575173382-Bromo-5-chloro-4-(dimethoxymethyl)pyridine

生成物 1

HCID 667628875-Chloro-4-(dimethoxymethyl)-2-(3-methoxypropyl)pyridine収率 62%

試薬・触媒・溶媒 2

HCID 178418745HCID 178418745、化合物触媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a suspension of Mg (911 mg, 37.5 mmol) and iodine (one crystal) in dry THF (30 mL) was added dropwise 5% of the total amount of 1-bromo-3-methoxypropane (4.59 g, 30.0 mmol). The mixture was heated to reflux with the help of a heat gun until the Grignard-formation started. The rest of the 1-bromo-3-methoxypropane was added slowly, while an exothermic reaction proceeded. After the end of the addition, the reaction mixture was stirred under reflux for 20 min, and was allowed to cool to rt. This Grignard-sol. (1M in THF, 23.5 mL, 23.5 mmol) was added dropwise to a mixture of 2-bromo-5-chloro-4-dimethoxymethyl-pyridine (2.50 g, 9.38 mmol) and Ni(dppp)Cl2 (495 mg, 0.938 mmol) in THF (50 mL) at 0° C. The reaction mixture was stirred at rt for 30 min, and was then heated to reflux for 2 h. The mixture was allowed to cool to rt, and was dissolved with EtOAc. This mixture was washed with aq. sat. NaHCO3. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (heptane→EtOAc/heptane 1:1) yielded the title compound (1.51 g, 62%). LC-MS: tR=0.80 min; ES+: 260.15.

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux with the help of a heat gun until the Grignard-formation
  3. additionAfter the end of the addition
  4. temperatureunder reflux for 20 min
  5. stirringThe reaction mixture was stirred at rt for 30 min
  6. temperaturewas then heated
  7. temperatureto reflux for 2 h
  8. temperatureto cool to rt
  9. washThis mixture was washed with aq. sat. NaHCO3
  10. dry with materiallayer was dried over MgSO4
  11. filtrationfiltered
  12. customthe solvents were removed under reduced pressure
  13. customPurification of the residue by FC (heptane→EtOAc/heptane 1:1)

出典と根拠

ORDレコード
ord-eabfb309d8f44a30b0a4325c777b7e87
出典データセット
uspto-grants-2011_06
特許番号
US07968720B2

反応ノート

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