2,6-Dichloropyridine → 2-Chloro-6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridine

HRID 1822004

반응식

HRID 1822004 반응식
[H-].[Na+].[CH:3]1([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]2)[CH2:5][CH2:4]1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Cl)[N:16]=1>CN(C=O)C>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:13][CH:10]2[CH2:11][CH2:12][N:7]([CH2:6][CH:3]3[CH2:4][CH2:5]3)[CH2:8][CH2:9]2)[N:16]=1

참가 물질

5

반응물 3

HCID 169892,6-DichloropyridineHCID 24758Sodium hydrideHCID 214287521-(Cyclopropylmethyl)piperidin-4-ol

생성물 1

HCID 578937202-Chloro-6-(1-cyclopropylmethyl-piperidin-4-yloxy)-pyridine수율 61%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Add NaH (60% dispersion in oil, 130 mg, 3.25 mmol) to a solution of 1-cyclopropylmethyl-piperidin-4-ol (preparation 11, 458 mg, 2.95 mmol) in DMF (8 mL) and stir for 20 min. Then add 2,6-dichloropyridine to the mixture and heat at 120° C. overnight. Quench the reaction with saturated NaHCO3, extract with methylene dichloride three times. Combine the organic layers, wash with saturated NaCl solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride provides 480 mg (61%) of the title compound: mass spectrum (ion spray): m/z=267.2 (M+1); 1H NMR (CDCl3, ppm): 7.39 (t, 1H), 6.75 (d, 1H), 6.52 (d, 1H), 4.96 (m, 1H), 2.75 (m, 2H), 2.30 (m, 2H), 2.19 (d, 2H), 1.97 (m, 2H), 1.75 (m, 2H), 0.76 (m, 1H), 0.43 (m, 2H), 0.00 (m, 2H).

후처리

  1. customQuench
  2. customthe reaction with saturated NaHCO3
  3. extractionextract with methylene dichloride three times
  4. washCombine the organic layers, wash with saturated NaCl solution
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue
  9. washChromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride

출처 및 근거

ORD 기록
ord-9cef1e8696f9412d89afe1c9b59298c5
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07608629B2

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