Hydrochloric Acid → HCID 54192310, compound

HRID 1755999Notes

Reaction equation

HRID 1755999 reaction equation
C([O:3][C:4](=[O:19])[CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)C.[Li+].CC([N-]C(C)C)C.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34]Cl)=[CH:32][CH:31]=1.[OH-].[Na+].Cl>C1COCC1.C(O)(C)C>[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][C:5]2([C:4]([OH:3])=[O:19])[CH2:6][CH2:7][N:8]([C:11](=[O:18])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:9][CH2:10]2)=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 699934-Methyloxybenzyl chlorideHCID 735824Ethyl 1-benzoylpiperidine-4-carboxylateHCID 2724682Lithium diisopropylamide

Product 1

HCID 54192310HCID 54192310, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of ethyl-N-benzoylisonipecotate (52 g, 0.2 mole) in THF (1 L) at -78° C. is treated with a solution of LDA in THF (110 mL of a 1 M solution). The solution is stirred at -78° for 15 minutes at which time 4-methoxybenzyl chloride (37.5 g, 0.22 moles) is added and the reaction warmed to room temperature over 2 hours. The reaction is concentrated at reduced pressure to @ one quarter volume and then poured into saturated aqueous sodium bicarbonate (1 L) and extracted with ethyl acetate (3×500 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The residue is chromatographed on silica gel with 30% ethyl acetate / hexane as eluent to give 66 g. The material thus obtained is dissolved in isopropyl alcohol (150 mL) and THF (150 mL) and treated with 10 N NaOH (250 mL). The mixture is heated to reflux for 48 hr. The reaction is cooled to room temperature and carefully neutralized by pouring over 1 L of crushed ice and adding 6 N HCl until pH 3. The mixture is then extracted with ethyl acetate (3×500 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure to give the product.

Workup

  1. additionis added
  2. concentrationThe reaction is concentrated at reduced pressure
  3. additionpoured into saturated aqueous sodium bicarbonate (1 L)
  4. extractionextracted with ethyl acetate (3×500 mL)
  5. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe residue is chromatographed on silica gel with 30% ethyl acetate / hexane as eluent
  9. customto give 66 g
  10. customThe material thus obtained
  11. temperatureThe mixture is heated
  12. temperatureto reflux for 48 hr
  13. temperatureThe reaction is cooled to room temperature
  14. extractionThe mixture is then extracted with ethyl acetate (3×500 mL)
  15. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated at reduced pressure
  18. customto give the product

Sources & evidence

ORD record
ord-2058b2fd2ae445a9a4ca6b021ffd0921
Source dataset
uspto-grants-1995_08
Patent number
US05439914

Reaction notes

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