Water → HCID 23312336, compound

HRID 745828Notes

Reaction equation

HRID 745828 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][CH:9]([C:12]3[O:13][C:14]4[CH:20]=[CH:19][C:18]([CH:21]5[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]5)=[CH:17][C:15]=4[CH:16]=3)[CH2:8][CH2:7]2)=O)[CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[CH:1]1([CH2:4][N:6]2[CH2:11][CH2:10][CH:9]([C:12]3[O:13][C:14]4[CH:20]=[CH:19][C:18]([CH:21]5[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]5)=[CH:17][C:15]=4[CH:16]=3)[CH2:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 23312333HCID 23312333, compound

Product 1

HCID 23312336HCID 23312336, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 19.0 g of 1-(cyclopropylcarbonyl)-4-(5-cyclohexyl-2-benzofuranyl)-piperidine in 150 ml of tetrahydrofuran is added dropwise to a solution, boiling under reflux, of 13.5 g of lithium aluminium hydride in 200 ml of tetrahydrofuran. The reaction mixture is then refluxed for a further 15 hours; it is afterwards cooled, and the unreacted lithium aluminium hydride is decomposed at -10° by means of 15 ml of water, 15 ml of 10% sodium hydroxide solution and 45 ml of water. The reaction solution is thereupon filtered with suction, the filter residue is washed with 100 ml of chloroform, and the combined filtrates are concentrated in vacuo. The residue is dissolved in 500 ml of 2N hydrochloric acid, and the acid solution is washed with ether. The aqueous solution is subsequently brought to pH 12 by the addition of 10% sodium hydroxide solution, and extracted with one liter of chloroform. The chloroform solution is dried with sodium sulphate, filtered with suction and concentrated by evaporation to obtain crude 1-(cyclopropylmethyl)-4-(5-cyclohexyl-2-benzofuranyl)-piperidine. This is converted with hydrogen chloride in ethyl acetate into the hydrochloride, and this is recrystallised from ethyl acetate, whereupon it melts at 220°.

Workup

  1. temperatureThe reaction mixture is then refluxed for a further 15 hours
  2. temperatureit is afterwards cooled
  3. filtrationThe reaction solution is thereupon filtered with suction
  4. washthe filter residue is washed with 100 ml of chloroform
  5. concentrationthe combined filtrates are concentrated in vacuo
  6. dissolutionThe residue is dissolved in 500 ml of 2N hydrochloric acid
  7. washthe acid solution is washed with ether
  8. additionThe aqueous solution is subsequently brought to pH 12 by the addition of 10% sodium hydroxide solution
  9. extractionextracted with one liter of chloroform
  10. dry with materialThe chloroform solution is dried with sodium sulphate
  11. filtrationfiltered with suction
  12. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-c04f1079e40442049f3f97ea26eff86e
Source dataset
uspto-grants-1986_07
Patent number
US04600719

Reaction notes

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