Sodium Hydroxide → 4-Hydroxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1-thia-8-aza-spiro[4.5]dec-3-en-2-one

HRID 2035310Notes

Reaction equation

HRID 2035310 reaction equation
C[O:2][C:3](=O)[CH:4]([C:25]1[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:26]=1[CH3:33])[C:5]([C:7]1([S:15]CC2C=CC(OC)=CC=2)[CH2:12][CH2:11][N:10]([O:13][CH3:14])[CH2:9][CH2:8]1)=[O:6].[OH-].[Na+]>FC(F)(F)C(O)=O.O>[OH:6][C:5]1[C:7]2([CH2:8][CH2:9][N:10]([O:13][CH3:14])[CH2:11][CH2:12]2)[S:15][C:3](=[O:2])[C:4]=1[C:25]1[C:30]([CH3:31])=[CH:29][C:28]([CH3:32])=[CH:27][C:26]=1[CH3:33]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 667938903-[1-Methoxy-4-(4-methoxy-benzylsulfanyl)-piperidin-4-yl]-3-oxo-2-(2,4,6-trimethylphenyl)-propionic acid methyl ester

Product 1

HCID 1363406794-Hydroxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1-thia-8-aza-spiro[4.5]dec-3-en-2-oneYield 48.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

470 mg 3-[1-Methoxy-4-(4-methoxy-benzylsulfanyl)-piperidin-4-yl]-3-oxo-2-(2,4,6-trimethylphenyl)-propionic acid methyl ester (from Step 6) was dissolved in 15 ml trifluoroacetic acid and heated on reflux for 18 hours. The mixture was cooled to room temperature, diluted with water, the pH adjusted to 4.2 by the addition of aqueous sodium hydroxide, then extracted with t-butylmethyl ether. The organic layer was dried over anhydrous sodium sulfate, and the solvent evaporated. The residue was chromatographed on silica gel with ethyl acetate/cyclohexane (1:1, then 2:1) as a solvent, to yield 156 mg 4-hydroxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1-thia-8-aza-spiro[4.5]dec-3-en-2-one (compound P2.4) as a solid, mp 67-71° C.

Workup

  1. temperatureheated
  2. temperatureon reflux for 18 hours
  3. extractionextracted with t-butylmethyl ether
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent evaporated
  6. customThe residue was chromatographed on silica gel with ethyl acetate/cyclohexane (1:1

Sources & evidence

ORD record
ord-76b3d1afc8f14697b4904bd2f88c15b0
Source dataset
uspto-grants-2013_11
Patent number
US08574607B2

Reaction notes

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