Methanol → 1-Dimethylamino-4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

HRID 2367892Notes

Reaction equation

HRID 2367892 reaction equation
[C:1]([C:3]1([N:12]([OH:25])[C:13](=[O:24])[CH2:14][C:15]2[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=2[CH3:23])[CH2:8][CH2:7][N:6]([N:9]([CH3:11])[CH3:10])[CH2:5][CH2:4]1)#N.S(=O)(=O)(O)[OH:27].[CH3:31][OH:32]>>[CH3:31][O:32][C:1]([C:3]1([N:12]([OH:25])[C:13](=[O:24])[CH2:14][C:15]2[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=2[CH3:23])[CH2:8][CH2:7][N:6]([N:9]([CH3:11])[CH3:10])[CH2:5][CH2:4]1)=[O:27]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 86671306N-(4-Cyano-1-dimethylamino-piperidin-4-yl)-N-hydroxy-2-(2,4,6-trimethyl-phenyl)-acetamide

Product 1

HCID 866713071-Dimethylamino-4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Conditions

Temperature
60 °C

Procedure

4.5 g N-(4-Cyano-1-dimethylamino-piperidin-4-yl)-N-hydroxy-2-(2,4,6-trimethyl-phenyl)-acetamide (from Step 3) is dissolved in 60 ml methanol. Then, 6.4 g concentrated sulfuric acid is added slowly. The mixture is heated to 60° C. for 2 days, then cooled to ambient temperature, and the solvent evaporated. The residue is partitioned with water and ethyl acetate, the organic layer is separated, washed with brine, dried over sodium sulfate, and the solvent is evaporated. The residue is purified by chromatography on silica gel, with ethyl acetate containing 7.5% triethylamine as a solvent. Thus, 1.35 g 1-Dimethylamino-4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester is obtained. 1H-NMR (CDCl3): 7.90 ppm (s, broad, 1H), 6.84 ppm (s, 2H), 3.86 ppm (s, 2H), 3.71 ppm (s, 3H), 2.80 ppm (m, 2H), 2.70 ppm (m, 2H), 2.53 ppm (m, 2H), 2.40 ppm (s, 6H), 2.23 ppm (s, 3H), 2.22 ppm (s, 6H), 2.15 ppm (m, 2H).

Workup

  1. temperaturecooled to ambient temperature
  2. customthe solvent evaporated
  3. customThe residue is partitioned with water and ethyl acetate
  4. customthe organic layer is separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. customthe solvent is evaporated
  8. customThe residue is purified by chromatography on silica gel, with ethyl acetate containing 7.5% triethylamine as a solvent

Sources & evidence

ORD record
ord-233780d46d8c4897a427c9d636b5fd19
Source dataset
uspto-grants-2014_04
Patent number
US08703165B2

Reaction notes

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