Dimethylformamide → 2-Chloro-4-(chloromethyl)-3-methylpyridine

HRID 1355522Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1355522
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([CH2:9]O)[CH:5]=[CH:4][N:3]=1.CN(C=O)C.O=P(Cl)(Cl)[Cl:18]>C(Cl)Cl>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([CH2:9][Cl:18])[CH:5]=[CH:4][N:3]=1

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 22504279(2-Chloro-3-methylpyridin-4-yl)methanol

Produkt 1

HCID 185068432-Chloro-4-(chloromethyl)-3-methylpyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(2-Chloro-3-methyl-pyridin-4-yl)-methanol (12-4, impure, 0.200 g) was dissolved in 5 mL anhydrous DCM under N2. Anhydrous DMF (0.098 mL, 1.3 mmol) and POCl3 (0.118 mL, 1.27 mmol) were added and the reaction was stirred at RT for 17 h. The reaction was quenched with sat NaHCO3 (aq) and extracted 3× with DCM. The organic phases were dried over Na2SO4, filtered and concentrated to provide 2-chloro-4-chloromethyl-3-methyl-pyridine still contaminated with a major by-product. 2-Chloro-4-chloromethyl-3-methyl-pyridine (impure, 0.215 g) was stirred in 3 mL DMSO. 1-Acetylpiperazine (0.626 g, 4.88 mmol was added and the reaction was stirred at RT overnight. The solution was purified by directly loading onto a preparative reverse phase column to afford an oil which slowly crystallizes. TFA salt: 1H NMR (CD3OD) δ 8.30 (d, 1H, J=5.0 Hz), 7.53 (d, 1H, J=5.0 Hz), 4.48 (s, 2H), 3.84 (bs, 4H), 3.39-3.30 (m, 4H), 2.14 (s, 3H).

Aufarbeitung

  1. customThe reaction was quenched with sat NaHCO3 (aq)
  2. extractionextracted 3× with DCM
  3. dry with materialThe organic phases were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-5e4e5ca230a040e797fb51f855968594
Quelldatensatz
uspto-grants-2003_07
Patentnummer
US06586424B2

Notizen zur Reaktion

Wird geladen…