Hydrochloric Acid → HCID 15462781, compound

HRID 1862220Notes

Reaction equation

HRID 1862220 reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.CC([Li])CC.[N:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C:16](=[O:22])[CH2:15]2.Cl>O1CCCC1.C1CCCCC1.O>[OH:8][C:7]1[C:2]([CH2:1][C:16]2([OH:22])[CH:17]3[CH2:20][CH2:21][N:14]([CH2:19][CH2:18]3)[CH2:15]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 195073-QuinuclidinoneHCID 707192-Methylpyridin-3-olHCID 178418400CID 53628100

Product 1

HCID 15462781HCID 15462781, compoundYield 55.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-56 °C

Procedure

52.9 g (484 mmol) of 2-methyl-3-hydroxypyridine dissolved in 1300 ml of tetrahydrofuran are introduced into a 2000 ml three-neck flask under argon. The solution is cooled to −56° C. and 750 ml (975 mmol) of a 1.3 M 1-methylpropyllithium solution in cyclohexane is added dropwise in the course of 3 h, keeping the temperature lower than −50° C. At the end of the addition, the temperature is allowed to rise to −4° C. in the course of 45 min and the mixture is then again cooled to −58° C. to add 60.6 g (484 mmol) of 1-azabicyclo[2.2.2]octan-3-one dissolved in 250 ml of tetrahydrofuran dropwise in the course of 40 min. The temperature is allowed to rise to ambient and stirring is maintained for 20 h. The reaction mixture is cooled to 4° C. and hydrolysed by addition of 110 ml of an aqueous solution of 36% hydrochloric acid. 400 ml of water are added, the two phases are allowed to settle and the organic phase is extracted with water. The aqueous phases are reunited, the mixture is cooled to 4° C. and a concentrated aqueous solution of sodium hydroxide is added to pH 8.4. The precipitate obtained is filtered and dried in vacuo at 80° C. 62.5 g of product are thus obtained.

Workup

  1. additionare introduced into a 2000 ml three-neck flask under argon
  2. customlower than −50° C
  3. additionAt the end of the addition
  4. customto rise to −4° C. in the course of 45 min
  5. temperaturethe mixture is then again cooled to −58° C.
  6. temperatureis maintained for 20 h
  7. extractionthe organic phase is extracted with water
  8. temperaturethe mixture is cooled to 4° C.
  9. additiona concentrated aqueous solution of sodium hydroxide is added to pH 8.4
  10. customThe precipitate obtained
  11. filtrationis filtered
  12. customdried in vacuo at 80° C

Sources & evidence

ORD record
ord-09f1d581e0874d9e9587564f35c2b99b
Source dataset
uspto-grants-2003_03
Patent number
US06538003B1

Reaction notes

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