Hydrochloric Acid → 1-(4-Benzyloxy-benzenesulfonyl)-5-methoxy-piperidine-2-carboxylic acid

HRID 2269317Notes

Reaction equation

HRID 2269317 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([N:18]2[CH2:23][CH:22]([OH:24])[CH2:21][CH2:20][CH:19]2[C:25]([OH:27])=[O:26])(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:31].Cl>C1COCC1.CN1CCCC1=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([S:15]([N:18]2[CH2:23][CH:22]([O:24][CH3:31])[CH2:21][CH2:20][CH:19]2[C:25]([OH:27])=[O:26])(=[O:16])=[O:17])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 181794331-(4-Benzyloxy-benzenesulfonyl)-5-hydroxy-piperidine-2-carboxylic acid

Product 1

HCID 183337301-(4-Benzyloxy-benzenesulfonyl)-5-methoxy-piperidine-2-carboxylic acidYield 75%

Reagents, catalysts & solvents 1

HCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Procedure

A mixture of 1-(4-benzyloxy-benzenesulfonyl)-5-hydroxy-piperidine-2-carboxylic acid (0.10 g, 0.26 mmol) and 1:1 THF-N-methylpyrrolidin-2-one (1 mL) was treated with NaH (0.031 g, 0.78 mmol, 60% dispersion in mineral oil). After stirring for 10 min, the mixture was warmed to room temperature, stirred for 20 min and treated with iodomethane (0.016 mL, 0.26 mmol). After stirring fro 3 h, the mixture was treated with an additional 0.010 g of NaH and 0.015 mL of iodomethane. The resulting mixture was stirred for 24 h, acidified with 1M HCl, extracted 3× with ethyl acetate, and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue by radial chromatography (1:1 to 2:1 ethyl acetate hexane containing 1% of acetic acid, 2 mm silica gel plate) afforded 0.077 g (75%) of 1-(4-benzyloxy-benzenesulfonyl)-5-methoxy-piperidine-2-carboxylic acid as a colorless syrup:

Workup

  1. stirringstirred for 20 min
  2. stirringAfter stirring fro 3 h
  3. stirringThe resulting mixture was stirred for 24 h
  4. extractionextracted 3× with ethyl acetate
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by radial chromatography (1:1 to 2:1 ethyl acetate hexane containing 1% of acetic acid, 2 mm silica gel plate)

Sources & evidence

ORD record
ord-6a32425d6c0d406d8c71749fd90a7ec1
Source dataset
uspto-grants-2001_12
Patent number
US06329397B1

Reaction notes

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