Acetaldehyde → HCID 10397613, compound

HRID 2426501Notes

Reaction equation

HRID 2426501 reaction equation
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:27])[CH3:26].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:27])[CH3:26])[CH:22]=1

Participants

10

Reactant 6

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 130352,2,6,6-TetramethylpiperidineHCID 744033-Chloro-6-methoxypyridazineHCID 516892Sodium BicarbonateHCID 178418339Butyllithium

Product 1

HCID 10397613HCID 10397613, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

47.7 ml of a 1.6M solution of n-Butyl lithium in hexane is added dropwise at −75° C. to 100 ml tetrahydrofuran followed by 12.9 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 5 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 23.5 ml acetaldehyde in 50 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 25 ml concentrated aqueous HCl, 100 ml ethanol and 125 ml tetrahydrofuran is added and the mixture is allowed to warm to room temperature. 60 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 3.85 g. LC-MS (ES+) 189 (M+H)+. NMR analysis indicates that the product contained approximately 15% of 1-(3-Chloro-6-methoxy-pyridazin-4-yl)-ethanol.

Workup

  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

Sources & evidence

ORD record
ord-5155165191bf47a085be8233a960ad34
Source dataset
uspto-grants-2011_06
Patent number
US07968546B2

Reaction notes

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