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

HRID 1355522ノート

反応式

HRID 1355522 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(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).

後処理

  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

出典と根拠

ORDレコード
ord-5e4e5ca230a040e797fb51f855968594
出典データセット
uspto-grants-2003_07
特許番号
US06586424B2

反応ノート

読み込み中…