Triethylamine → 1-benzyl-N-hydroxy-4-(4-methoxyphenylsulfonyl)piperidine-4-carboxamide

HRID 565334Notes

Reaction equation

HRID 565334 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2([C:25]([OH:27])=O)[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:35][OH:36].C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl.C1COCC1.O>[OH:36][NH:35][C:25]([C:12]1([S:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)(=[O:11])=[O:10])[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][CH2:13]1)=[O:27]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 443297Hydroxyamine hydrochlorideHCID 111436104-(4-Methoxy-benzenesulfonyl)-1-benzyl-piperidine-4-carboxylic acid

Product 1

HCID 98659361-benzyl-N-hydroxy-4-(4-methoxyphenylsulfonyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a stirred solution of 4-(4-Methoxy-benzenesulfonyl)-1-benzyl-piperidine-4-carboxylic acid (2.0 g, 5.1 mmol) and DMF (2 drops) in CH2Cl2 (100 ml) at 0° C., oxalyl chloride (1.0 gm, 8 mmol) was added in a drop-wise manner. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, in a separate flask a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) was stirred in THF:water (5:1, 30 ml) at 0° C. for 1 hour. At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH2Cl2 and added slowly to the hydroxylamine at 0° C. The reaction mixture was stirred at room temperature for 24 hours and concentrated. The residue obtained was extracted with chloroform and washed well with water. The product obtained was purified by silica gel column chromatography and eluted with chloroform the product 4-(4-Methoxy-benzenesulfonyl)-1-benzyl-piperidine-4-carboxylic acid hydroxyamide was isolated as a colorless solid. mp 90-95° C.; Yield, 1.2 g, 48%; MS: 405 (M+H)+; 1H NMR (300 MHz, DMSO-d6): δ 2.29 (m, 3H), 2.76-2.79 (m, 2H), 3.43 (m, 4H),4.30 (s, 2H), 7.14-7.17 (d,2H), 7.50-7.73 (m, 5H), 9.37 (s,1H), 10.53 (s,1H), 11.18 (s,1H).

Workup

  1. additionAfter the addition
  2. concentrationwas concentrated
  3. dissolutionthe pale yellow residue was dissolved in 10 ml of CH2Cl2
  4. additionadded slowly to the hydroxylamine at 0° C
  5. stirringThe reaction mixture was stirred at room temperature for 24 hours
  6. concentrationconcentrated
  7. customThe residue obtained
  8. extractionwas extracted with chloroform
  9. washwashed well with water
  10. customThe product obtained
  11. customwas purified by silica gel column chromatography
  12. washeluted with chloroform the product 4-(4-Methoxy-benzenesulfonyl)-1-benzyl-piperidine-4-carboxylic acid hydroxyamide
  13. customwas isolated as a colorless solid
  14. customYield

Sources & evidence

ORD record
ord-e8d50fb744954b05911094f7b9974ad9
Source dataset
uspto-grants-2001_01
Patent number
US06172057B2

Reaction notes

Loading…