Sodium Bicarbonate → 4-[5-carbomethoxymethyl-1H-indol-3-yl]N-methylpiperidine

HRID 1034468Notes

Reaction equation

HRID 1034468 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH:9]=O)[CH2:4][CH2:3]1.Cl.[CH2:12]([O:14][C:15]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24]N)=[CH:20][CH:19]=1)=[O:16])C.C(=O)(O)[O-].[Na+]>CO.O>[C:15]([CH2:17][C:18]1[CH:23]=[C:22]2[C:21](=[CH:20][CH:19]=1)[NH:24][CH:9]=[C:8]2[CH:5]1[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]1)([O:14][CH3:12])=[O:16]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 21254104Ethyl (4-hydrazinophenyl)acetate hydrochlorideHCID 21666286(1-Methylpiperidin-4-yl)acetaldehyde

Product 1

HCID 190230094-[5-carbomethoxymethyl-1H-indol-3-yl]N-methylpiperidineYield 39.3%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of 1-methyl-4 (formylmethyl)piperidine (2.3 g, 16 mmol) and 4-(ethoxycarbonylmethyl)phenyl hydrazine hydrochloride (3.7 g, 16 mmol) in methanol:water (20:1) (25 ml) was stirred at room temperature for 1 hour. Polyphosphoric acid (7 g) was then added and the mixture heated at reflux for 5 hours, under nitrogen. The mixture was then cooled to ambient temperature, basified with saturated sodium bicarbonate to pH9, and extracted with dichloromethane (2×20 ml). The organic phases were combined, dried (MgSO4) and evaporated to give a brown residue. This was chromatographed (eluant 50:8:1 dichloromethane:ethanol:ammonia) to give 4-[5-carbomethoxymethyl-1H-indol-3-yl]N-methylpiperidine (1.8 g, 39%) as a yellow solid. mp 105°-107° C. δ(360 MHz, CDCl3) δ1.85 (2H, m), 2.16 (4H, m), 2.36 (3H, s), 2.81 (1H, m), 3.00 (2H, m), 3.70 (3H, s), 3.73 (2H, s), 6.97 (1H, d, J=2 Hz), 7.10 (1H, dd, J=8 and Hz), 7.31 (1H, d, J=8 Hz), 7.53 (1H, s), 7.97 (1H, brs).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 5 hours, under nitrogen
  3. extractionextracted with dichloromethane (2×20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give a brown residue
  7. customThis was chromatographed (eluant 50:8:1 dichloromethane:ethanol:ammonia)

Sources & evidence

ORD record
ord-80c06096d43a49c7a85031d16621d86d
Source dataset
uspto-grants-1994_05
Patent number
US05317103

Reaction notes

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