Acetyl chloride → N-(1-cyano-4-(4-ethoxy-3-methylphenylsulfonamido)cyclohexyl)acetamide

HRID 1944742Notes

Reaction equation

HRID 1944742 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C:6]1([C:26]#[N:27])[CH2:11][CH2:10][CH:9]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH3:24])=[C:18]([CH3:25])[CH:17]=2)(=[O:15])=[O:14])[CH2:8][CH2:7]1.C(OCC)(=O)C>ClCCl.CCCCCCC>[C:26]([C:6]1([NH:5][C:1](=[O:3])[CH3:2])[CH2:7][CH2:8][CH:9]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH3:24])=[C:18]([CH3:25])[CH:17]=2)(=[O:14])=[O:15])[CH2:10][CH2:11]1)#[N:27]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 67224098HCID 67224098, compound2×

Product 1

HCID 67223797N-(1-cyano-4-(4-ethoxy-3-methylphenylsulfonamido)cyclohexyl)acetamideYield 77.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8900HeptaneSolvent

Procedure

Acetyl chloride (0.106 g, 1.356 mmol) in dichloromethane (1 ml) was added to room temperature solution of N-(4-amino-4-cyanocyclohexyl)-4-ethoxy-3-methylbenzenesulfonamide (Intermediate 124, 0.366 g, 1.085 mmol) in dichloromethane (9 ml) and the reaction was stirred 18 hours. The reaction was diluted with dichloromethane and rinsed with two volumes of saturated sodium bicarbonate. The organics were dried over magnesium sulfate, filtered, and concentrated to yield 464 mg of a crude film. TLC (50% ethyl acetate in heptane) indicated a major spot Rf=0.07 by UV. The crude product was chromatographed on Biotage 25S by TLC generated gradient to yield N-(1-cyano-4-(4-ethoxy-3-methylphenylsulfonamido)cyclohexyl)-acetamide (320 mg, 0.843 mmol) as a colorless solid. Carbon-13 NMR displayed a characteristic signature for nitrile at 119.1 ppm along with a signal at 110.7 ppm for the aromatic carbon ortho to aryl ether; in addition the peaks at 169.7 ppm and 160.97 ppm represent the amide and ipso-carbon of the aryl ether (no assignment implied). LCMS [M+H]=380.2.

Workup

  1. washrinsed with two volumes of saturated sodium bicarbonate
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto yield 464 mg of a crude film
  6. customThe crude product was chromatographed on Biotage 25S by TLC

Sources & evidence

ORD record
ord-e5d23d4e28784654ac9828b58249dabd
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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