Sodium hydride → HCID 20306016, compound

HRID 1732340Notes

Reaction equation

HRID 1732340 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].[CH2:13]([O:15][CH:16]([O:19][CH2:20][CH3:21])[CH2:17]Br)[CH3:14]>>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][CH2:17][CH:16]([O:19][CH2:20][CH3:21])[O:15][CH2:13][CH3:14])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 24758Sodium hydride2×HCID 74852Ethane, 2-bromo-1,1-diethoxy-2×HCID 107492911-(4-Hydroxypiperidin-1-yl)ethan-1-one

Product 1

HCID 20306016HCID 20306016, compoundYield 59.4%

Procedure

N-Acetyl-4-hydroxypiperidine (57.2 g.) in dry D.M.F. (250 ml.) was added dropwise to a stirred suspension of sodium hydride (23.2 g., 50% dispersion in mineral oil) in dry D.M.F. (200 ml.) under an atmosphere of nitrogen and with external cooling in an ice/water bath. The suspension was allowed to warm to room temperature then stirred for 5 hours. Bromoacetaldehyde diethylacetal (94.7 g.) was added slowly to the stirred reaction mixture with cooling then the mixture was stirred at room temperature for 18 hours. A further quantity of sodium hydride (23.2 g.) was added portionwise and stirring continued until effervescence had ceased. A further 100 ml. dry D.M.F. was added and the mixture cooled in an ice/water bath while a second batch of bromoacetaldehyde diethylacetal (94.7 g.) was slowly added. The mixture was stirred at room temperature for 3 hours then isopropopanol (150 ml.) added to destroy excess sodium hydride. The suspension was filtered, the filtrate concentrated under reduced pressure then the residue taken up in water and extracted with chloroform. The chloroform extract was dried (Na2SO4), the solvent evaporated in vacuo and the residue distilled to give N-acetyl-4-(2,2-diethoxyethoxy)piperidine (61.5 g.), b.p. 142°-145° C./3 mm., characterized by n.m.r.

Workup

  1. temperature(200 ml.) under an atmosphere of nitrogen and with external cooling in an ice/water bath
  2. temperaturewith cooling
  3. stirringthe mixture was stirred at room temperature for 18 hours
  4. stirringstirring
  5. additionwas added
  6. additionwas slowly added
  7. stirringThe mixture was stirred at room temperature for 3 hours
  8. additionadded
  9. customto destroy excess sodium hydride
  10. filtrationThe suspension was filtered
  11. concentrationthe filtrate concentrated under reduced pressure
  12. extractionextracted with chloroform
  13. extractionThe chloroform extract
  14. dry with materialwas dried (Na2SO4)
  15. customthe solvent evaporated in vacuo
  16. distillationthe residue distilled

Sources & evidence

ORD record
ord-c5f8e98cdaff4f45914effb1e5231d1c
Source dataset
uspto-grants-1980_12
Patent number
US04237138

Reaction notes

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