Piperidine → N-[2-Chloro-4-(piperidinosulphonyl)phenyl]-2-hydroxy-2-methylpropanamide

HRID 433330Notes

Reaction equation

HRID 433330 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([S:8](F)(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C:13](=[O:21])[C:14]([O:17]C(=O)C)([CH3:16])[CH3:15].[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.O.[OH-].[Li+].CCOC(C)=O>CN(C)C1C=CN=CC=1.C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:8]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)(=[O:9])=[O:10])[CH:5]=[CH:4][C:3]=1[NH:12][C:13](=[O:21])[C:14]([OH:17])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 8082PiperidineHCID 8857Ethyl AcetateHCID 168937Lithium hydroxide, monohydrateHCID 18758703N-(2-Chloro-4-fluorosulphonylphenyl)-2-acetoxy-2-methylpropanamide

Product 1

HCID 18758611N-[2-Chloro-4-(piperidinosulphonyl)phenyl]-2-hydroxy-2-methylpropanamideYield 60%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of N-[2-chloro-4-(fluorosulphonyl)phenyl]-2-acetoxy-2-methylpropanamide (Method B) (340 mg, 1 mmol), 4-dimethylaminopyridine (10 mg, 0.08 mmol) and piperidine (0.1 ml, 1 mmol) in acetonitrile (5 ml) was heated under reflux for 18 h. After evaporation to dryness, the residue was dissolved in 1% aqueous ethanol (10 ml) and lithium hydroxide monohydrate (84 mg, 2 mmol) was added. The mixture was stirred for 2 h at ambient temperature, then EtOAc (25 ml) was added. The resulting solution was washed with water, dried and evaporated to dryness. The residue was purified by column chromatography using 50% EtOAc/isohexane to yield the title compound as an oil (226 mg, 0.6 mmol). NMR: 1.4 (s, 6H), 1.5 (m, 6H), 2.9 (m, 4H), 6.2 (d, 1H), 7.7 (d, 1H), 7.8 (m, 1H), 8.6 (d, 1H), 9.8 (s, 1H); MS: 361 (M+H)+.

Workup

  1. temperatureunder reflux for 18 h
  2. customAfter evaporation to dryness
  3. dissolutionthe residue was dissolved in 1% aqueous ethanol (10 ml)
  4. washThe resulting solution was washed with water
  5. customdried
  6. customevaporated to dryness
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-43d739b5dbb44386bfe03e5fc9d45ef6
Source dataset
uspto-grants-2003_12
Patent number
US06667342B1

Reaction notes

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