4-Methylmorpholine → N-[2-(2,3-Dimethylphenoxy)-1-methylethyl)-N-methyl-2-(4-methanesulfonamido-phenyl)-acetamide

HRID 1386475Notes

Reaction equation

HRID 1386475 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=1)(=[O:4])=[O:3].CN1CCOCC1.ClC(OCC(C)C)=O.[CH3:31][NH:32][CH:33]([CH3:44])[CH2:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH3:42])[C:37]=1[CH3:43]>CN(C)C=O.C(N(CC)CC)C>[CH3:43][C:37]1[C:38]([CH3:42])=[CH:39][CH:40]=[CH:41][C:36]=1[O:35][CH2:34][CH:33]([N:32]([CH3:31])[C:13](=[O:15])[CH2:12][C:9]1[CH:8]=[CH:7][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:11][CH:10]=1)[CH3:44]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2773887{4-[(Methanesulfonyl)amino]phenyl}acetic acidHCID 21182036N-methyl-2-(2,3-dimethylphenoxy)-1-methylethylamine

Product 1

HCID 21182026N-[2-(2,3-Dimethylphenoxy)-1-methylethyl)-N-methyl-2-(4-methanesulfonamido-phenyl)-acetamideYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution containing 0.80 g (3.5 mmol) of 4-methanesulfonamido-phenylacetic acid (Example 32) in 20 ml of N,N-dimethylformamide (DMF) 0.46 ml (0.42 g, 4,2 mmol) of 4-methylmorpholine is added, the mixture is cooled to −10° C. and 0.65 ml (0.70 g, 5 mmol) of isobutyl chloroformate is added. After 10 minutes a solution containing 0.68 g (3.5 mmol) of N-methyl-2-(2,3-dimethylphenoxy)-1-methylethylamine (Example 44) in 3 ml of DMF pre-cooled to −10° C. is added, then the pH value of the mixture is adjusted to 8.5 by adding triethylamine. The reaction mixture is stirred at −10° C. for 1 hour, then at 0° C. for 1 hour. Then, the solvent is evaporated under reduced pressure and the solid residue is alkalinized by adding aqueous ammonia solution and distributed between water and ethyl acetate. The aqueous phase is washed twice with ethyl acetate, the combined organic phase is washed once with water, dried over sodium sulphate and evaporated. Thus, 1.13 g of the title substance are obtained as an amorphous substance, which is suitable to the next step without further purification. Yield: 80%.

Workup

  1. additionis added
  2. temperaturepre-cooled to −10° C.
  3. additionis added
  4. waitat 0° C. for 1 hour
  5. customThen, the solvent is evaporated under reduced pressure
  6. additionby adding aqueous ammonia solution
  7. washThe aqueous phase is washed twice with ethyl acetate
  8. washthe combined organic phase is washed once with water
  9. dry with materialdried over sodium sulphate
  10. customevaporated
  11. customThus, 1.13 g of the title substance are obtained as an amorphous substance, which
  12. customis suitable to the next step without further purification

Sources & evidence

ORD record
ord-a883dd220fbf468a82b9a09bd71b29d4
Source dataset
uspto-grants-2001_07
Patent number
US06265445B1

Reaction notes

Loading…