Formaldehyde → ethyl N-(4-fluoroindol-3-ylmethyl)piperidin-4-ylcarboxylate

HRID 866079Notes

Reaction equation

HRID 866079 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.C=O.[F:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH:17]=[CH:18][NH:19]2.[C:24](=O)(O)[O-].[Na+]>O1CCOCC1.C(O)(=O)C>[F:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17]([CH2:24][N:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1)=[CH:18][NH:19]2

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 70770Ethyl 4-piperidinecarboxylateHCID 516892Sodium BicarbonateHCID 27745024-Fluoroindole

Product 1

HCID 19040931ethyl N-(4-fluoroindol-3-ylmethyl)piperidin-4-ylcarboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A stirred solution of 1.8 grams (0.011 mole) of ethyl piperidin-4-ylcarboxylate in 10 mL of dioxane was cooled to 0° C., and 10 mL of acetic acid, followed by 0.9 mL of aqueous 37% formaldehyde were added. To this was then slowly added a solution of 1.5 grams (0.011 mole) of 4-fluoroindole in 10 mL of dioxane. Upon completion of the addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for about five hours. After this time the reaction mixture was again cooled to 0° C., and neutralized with an aqueous solution saturated with sodium bicarbonate. The mixture was extracted with two 100 mL portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium chloride, dried with sodium sulfate, and filtered. The filtrate was then passed through a pad of silica gel. The eluate was concentrated under reduced pressure, yielding 1.2 grams of ethyl N-(4-fluoroindol-3-ylmethyl)piperidin-4-ylcarboxylate, mp 96°-105° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionwere added
  2. additionUpon completion of the addition
  3. temperatureAfter this time the reaction mixture was again cooled to 0° C.
  4. extractionThe mixture was extracted with two 100 mL portions of diethyl ether
  5. washThe combined extracts were washed with an aqueous solution saturated with sodium chloride
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationThe eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-c3f125dba3b44708bde7abc465986468
Source dataset
uspto-grants-1996_10
Patent number
US05569664

Reaction notes

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