Hydrochloric Acid → Methyl 2,4-dimethyl-3-[[2-methyl-5-(4-oxo-1-piperidyl)benzoyl]amino]benzoate

HRID 239953Notes

Reaction equation

HRID 239953 reaction equation
O1[C:5]2([CH2:10][CH2:9][N:8]([C:11]3[CH:12]=[CH:13][C:14]([CH3:32])=[C:15]([CH:31]=3)[C:16]([NH:18][C:19]3[C:20]([CH3:30])=[C:21]([CH:26]=[CH:27][C:28]=3[CH3:29])[C:22]([O:24][CH3:25])=[O:23])=[O:17])[CH2:7][CH2:6]2)[O:4]CC1.Cl>C1COCC1>[CH3:30][C:20]1[C:19]([NH:18][C:16](=[O:17])[C:15]2[CH:31]=[C:11]([N:8]3[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]3)[CH:12]=[CH:13][C:14]=2[CH3:32])=[C:28]([CH3:29])[CH:27]=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86707339Methyl 3-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-2,4-dimethyl-benzoate

Product 1

HCID 86707338Methyl 2,4-dimethyl-3-[[2-methyl-5-(4-oxo-1-piperidyl)benzoyl]amino]benzoateYield 53.36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-2,4-dimethyl-benzoate (250 mg, 570.09 moles) in THF (2 ml) is added 4M HCl (1 ml) and stirred at ambient temperature. The mixture is concentrated under reduced pressure and re-dissolved in acetone (5 ml) followed by the addition of 5N HCl (1 ml). After 22 hours at 60° C., the mixture is cooled to ambient temperature and diluted with 2M NaOH to pH 6 and extracted twice with ethyl acetate. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 0-50% ethyl acetate in hexane to afford the title compound as an off-white foam (0.12 g, 53.36%). Mass spectrum (m/z): 395.2 (M+1).

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. dissolutionre-dissolved in acetone (5 ml)
  3. additionfollowed by the addition of 5N HCl (1 ml)
  4. temperaturethe mixture is cooled to ambient temperature
  5. additiondiluted with 2M NaOH to pH 6
  6. extractionextracted twice with ethyl acetate
  7. dry with materialThe combined organic layers are dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-a1f060202c4d4805a52542d5cd0a73f6
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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