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

HRID 1355459노트

반응식

HRID 1355459 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

(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) δ8.30 (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).

후처리

  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

출처 및 근거

ORD 기록
ord-bba2777b87084f7da3b6a3e2d44a5bf0
출처 데이터셋
uspto-grants-2003_07
특허 번호
US06586423B2

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