Hydrochloric Acid → 1-(6-Chloro-3-methoxy-pyridazin-4-yl)-propan-1-ol

HRID 1786693ノート

反応式

HRID 1786693 の反応式
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[N:18]=[N:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=1.[CH:25](=[O:28])[CH2:26][CH3:27].Cl.C(=O)(O)[O-].[Na+]>CCCCCC.O1CCCC1.C(O)C>[Cl:16][C:17]1[N:18]=[N:19][C:20]([O:23][CH3:24])=[C:21]([CH:25]([OH:28])[CH2:26][CH3:27])[CH:22]=1

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 527PropanalHCID 130352,2,6,6-TetramethylpiperidineHCID 744033-Chloro-6-methoxypyridazineHCID 516892Sodium BicarbonateHCID 178418339Butyllithium

生成物 1

HCID 102622801-(6-Chloro-3-methoxy-pyridazin-4-yl)-propan-1-ol

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒4 回HCID 8058Hexane溶媒

反応条件

温度
0 °C

実験手順

104.6 ml of a 1.6M solution of n-Butyl lithium in hexane is added dropwise at −75° C. to 200 ml tetrahydrofuran followed by 28.3 ml 2,2,6,6-tetramethylpiperidine and the resulting solution is allowed to warm to 0° C. and stirred for 30 min. The solution is cooled to −75° C. and a solution of 11 g 3-chloro-6-methoxypyridazine in 100 ml tetrahydrofuran is added at the same temperature. The reaction is stirred for 30 min at −75° C. A solution of 65.9 ml propionaldehyde in 200 ml tetrahydrofuran is cooled to −75° C. and added to the reaction. The solution is stirred at −75° C. for 90 min, then a mixture of 55 ml concentrated aqueous HCl, 220 ml ethanol and 275 ml tetrahydrofuran is added and the mixture is allowed to warm to room temperature. 150 ml of saturated aqueous sodium bicarbonate is slowly added, and the tetrahydrofuran is removed under reduced pressure. The resulting aqueous phase is extracted 3 times with dichloromethane. The organic phase is dried (MgSO4), filtered and evaporated under reduced pressure. The product is purified by silica gel chromatography, eluting with a gradient of ethyl acetate in heptane. Yield 12.25 g. LC-MS (ES+) 203 (M+H)+. NMR analysis indicated that the product contained approximately 15% of 1-(3-Chloro-6-methoxy-pyridazin-4-yl)-propan-1-ol.

後処理

  1. temperatureThe solution is cooled to −75° C.
  2. stirringThe reaction is stirred for 30 min at −75° C
  3. additionadded to the reaction
  4. stirringThe solution is stirred at −75° C. for 90 min
  5. additionis added
  6. temperatureto warm to room temperature
  7. customthe tetrahydrofuran is removed under reduced pressure
  8. extractionThe resulting aqueous phase is extracted 3 times with dichloromethane
  9. dry with materialThe organic phase is dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe product is purified by silica gel chromatography
  13. washeluting with a gradient of ethyl acetate in heptane

出典と根拠

ORDレコード
ord-eb075f340d53495fa1b59f44d7390793
出典データセット
uspto-grants-2009_03
特許番号
US07507734B2

反応ノート

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