Methanol → 1-Dimethylamino-4-{N',N'-dimethyl-N-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazino}-piperidine-4-carboxylic acid methyl ester

HRID 44134Notes

Reaction equation

HRID 44134 reaction equation
[C:1]([C:3]1([N:12]([C:16](=[O:27])[CH2:17][C:18]2[C:23]([CH3:24])=[CH:22][C:21]([CH3:25])=[CH:20][C:19]=2[CH3:26])[N:13]([CH3:15])[CH3:14])[CH2:8][CH2:7][N:6]([N:9]([CH3:11])[CH3:10])[CH2:5][CH2:4]1)#N.S(=O)(=O)(O)[OH:29].[CH3:33][OH:34]>>[CH3:33][O:34][C:1]([C:3]1([N:12]([C:16](=[O:27])[CH2:17][C:18]2[C:23]([CH3:24])=[CH:22][C:21]([CH3:25])=[CH:20][C:19]=2[CH3:26])[N:13]([CH3:15])[CH3:14])[CH2:8][CH2:7][N:6]([N:9]([CH3:11])[CH3:10])[CH2:5][CH2:4]1)=[O:29]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 67229472HCID 67229472, compound

Product 1

HCID 672274551-Dimethylamino-4-{N',N'-dimethyl-N-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazino}-piperidine-4-carboxylic acid methyl ester

Procedure

2.2 g (2,4,6-Trimethyl-phenyl)-acetic acid N-(4-cyano-1-dimethylamino-piperidin-4-yl)-N′,N′-dimethyl-hydrazide (from Step 3) is dissolved in 35 ml methanol and 8.7 g concentrated sulfuric acid is added dropwise. The mixture is heated to reflux for 18 hours, then cooled to room temperature, most of the solvent evaporated, then poured on ice, the pH adjusted to 7 by the addition of aqueous sodium hydroxide, and made alkaline by the addition of aqueous sodium bicarbonate. The mixture is then extracted with ethyl acetate, the organic layer dried over sodium sulfate and the solvent evaporated. The residue is chromatographed on silica gel with ethyl acetate/acetone (2:1) as a solvent, to give 1.55 g 1-Dimethylamino-4-{N′,N′-dimethyl-N-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazino}-piperidine-4-carboxylic acid methyl ester. 1H-NMR (CDCl3): 6.84 ppm (s, 2H), 3.70 ppm (s, 2H), 3.65 ppm (s, 3H), 3.05 ppm (s, 6H), 2.25 ppm (s, 3H), 2.21 ppm (s, 6H), 2.10-3.10 ppm (broad multiplets, total of 14H).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 18 hours
  3. customevaporated
  4. additionpoured on ice
  5. additionthe pH adjusted to 7 by the addition of aqueous sodium hydroxide
  6. additionby the addition of aqueous sodium bicarbonate
  7. extractionThe mixture is then extracted with ethyl acetate
  8. dry with materialthe organic layer dried over sodium sulfate
  9. customthe solvent evaporated
  10. customThe residue is chromatographed on silica gel with ethyl acetate/acetone (2:1) as a solvent

Sources & evidence

ORD record
ord-f242b37c75aa4aeebe84bf8d4a91b277
Source dataset
uspto-grants-2013_09
Patent number
US08541343B2

Reaction notes

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