Hydrochloric Acid → HCID 20343117, compound

HRID 2049997Notes

Reaction equation

HRID 2049997 reaction equation
Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl.[C-]#N.[K+].[OH-:20].[Na+].[O:22]1[CH2:26]CCC1.O>>[CH2:2]([N:9]1[CH2:14][CH2:13][CH2:12][C:11]([OH:15])([C:26]([OH:22])=[O:20])[CH2:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 5

HCID 313Hydrochloric Acid2×HCID 9032Potassium Cyanide2×HCID 14798Sodium HydroxideHCID 30849241-Benzyl-3-piperidone hydrochloride hydrateHCID 21881883Oxolane--water (1/1)

Product 1

HCID 20343117HCID 20343117, compoundYield 60.2%

Conditions

Temperature
80 °C

Procedure

To a solution of 8.13 g of 1-benzyl-3-piperidone hydrochloride in a mixture of 28.8 ml of tetrahydrofuran-water (1:1) and 2.99 ml (36 mmoles) of concentrated hydrochloric acid is added 4.687 g (72 mmoles) of potassium cyanide while keeping at a temperature below 8° C., and the mixture is stirred for 4 hours, additionally mixed with 1.495 ml (18 mmoles) of concentrated hydrochloric acid and 1.172 g (18 mmoles) of potassium cyanide, stirred for 1 hour and extracted with ether. The extract is washed with water, dried over magnesium sulfate, and evaporated under reduced pressure. The oily residue is dissolved in 14.4 ml of concentrated hydrochloric acid, heated at 80° C. for 1 hour, cooled and then filtered. The residue is washed with acetone. The combined filtrate and washing are evaporated under reduced pressure to yield syrupy residue, and the latter is adjusted to pH 8 with 0.25 N aqueous sodium hydroxide solution, washed thrice with chloroform, and slowly adsorbed on a column of 200 ml of Amberlite IR 120B (H+). The column is washed with 1 L of water, and the eluate with 1.28 L of 5 N aqueous sodium hydroxide solution is evaporated under reduced pressure. The residue is crystallized from acetone to yield 1-benzyl-3-hydroxypiperidine-3-carboxylic acid 1.3 hydrate (mp. 103.5°-104.5° C.) as prisms in 60.2% yield, and the latter is recrystallized from dimethylformamide-water-acetone to yield the pure crystalline product (mp. 104°-105° C.), and the latter is dried over phosphorus pentachloride at 70° C. for 48 hours to yield the corresponding anhydrous material (mp. 212°-214° C.).

Workup

  1. customwhile keeping at a temperature below 8° C.
  2. stirringstirred for 1 hour
  3. extractionextracted with ether
  4. washThe extract is washed with water
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. dissolutionThe oily residue is dissolved in 14.4 ml of concentrated hydrochloric acid
  8. temperaturecooled
  9. filtrationfiltered
  10. washThe residue is washed with acetone
  11. washThe combined filtrate and washing
  12. customare evaporated under reduced pressure
  13. customto yield syrupy residue
  14. washwashed thrice with chloroform
  15. washThe column is washed with 1 L of water
  16. customthe eluate with 1.28 L of 5 N aqueous sodium hydroxide solution is evaporated under reduced pressure
  17. customThe residue is crystallized from acetone

Sources & evidence

ORD record
ord-3c239b00c4d14c7c98e04f98095a1dba
Source dataset
uspto-grants-1980_04
Patent number
US04199570

Reaction notes

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