P-Toluenesulfonamide → 2-acetamido-2,3-dimethyl-N-(p-tolylsulfonyl)butyramide

HRID 275050Notes

Reaction equation

HRID 275050 reaction equation
[C:1]([NH:4][C:5]([CH3:12])([CH:9]([CH3:11])[CH3:10])[C:6]([OH:8])=O)(=[O:3])[CH3:2].C(OC(Cl)=O)C.[CH3:19][C:20]1[CH:21]=[CH:22][C:23]([S:26]([NH2:29])(=[O:28])=[O:27])=[CH:24][CH:25]=1.[Na]>C(N(CC)CC)C.C(OCC)C.CN(C)C=O>[C:1]([NH:4][C:5]([CH3:12])([CH:9]([CH3:11])[CH3:10])[C:6]([NH:29][S:26]([C:23]1[CH:24]=[CH:25][C:20]([CH3:19])=[CH:21][CH:22]=1)(=[O:27])=[O:28])=[O:8])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 6269P-ToluenesulfonamideHCID 10928Ethyl chloroformateHCID 2338052-Acetamido-2,3-dimethylbutanoic acidHCID 5360545Sodium

Product 1

HCID 146246882-acetamido-2,3-dimethyl-N-(p-tolylsulfonyl)butyramideYield 116.7%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

2-Acetamido-2,3-dimethylbutyric acid (1.5 g) is dissolved in a solution of triethylamine (2.7 g) in diethyl ether (50 mL) and cooled to 0° C.; ethylchloroformate (1.1 g) is added dropwise and the mixture is stirred at 0° to room temperature over one hour. The mixture is filtered, and the filtrate is concentrated in vacuo to afford the oily mixed anhydride (1.5 g). This material is mixed with 3 g of p-toluenesulfonamide, sodium salt, in 25 mL dimethylformamide, and the resulting mixture is heated at 80° C. for 16 hours. The reaction is cooled, concentrated in vacuo, and the residue is partitioned between methylene chloride and saturated, aqueous sodium bicarbonate. Acidification of the aqueous layer with conc. HCl to pH 1, extraction with CH2Cl2, drying, and stripping the organic phase affords the title product (3.3 g).

Workup

  1. filtrationThe mixture is filtered
  2. concentrationthe filtrate is concentrated in vacuo
  3. customto afford the
  4. temperaturethe resulting mixture is heated at 80° C. for 16 hours
  5. temperatureThe reaction is cooled
  6. concentrationconcentrated in vacuo
  7. customthe residue is partitioned between methylene chloride
  8. extractionAcidification of the aqueous layer with conc. HCl to pH 1, extraction with CH2Cl2
  9. customdrying

Sources & evidence

ORD record
ord-459db0b05ded459db5ab4ca5be40b901
Source dataset
uspto-grants-1995_02
Patent number
US05391757

Reaction notes

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