Pyridine → 1-[(3-Chloro-4-methanesulfonyl-phenyl)-(cyclohex-2-enyloxy)-acetyl]-3-methyl-urea

HRID 397200Notes

Reaction equation

HRID 397200 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH:19]=[CH:18]2)[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].FC1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.ClCCl.[CH3:39][NH:40][C:41]([NH2:43])=[O:42].N1C=CC=CC=1>C(OCC)(=O)C.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH:19]=[CH:18]2)[C:13]([NH:43][C:41]([NH:40][CH3:39])=[O:42])=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

9

Reactant 6

HCID 1049PyridineHCID 6344DichloromethaneHCID 10008FluorobenzeneHCID 11719MethylureaHCID 65578Oxalyl chlorideHCID 18172587Rac-(3-chloro-4-methanesulfonyl-phenyl)-(cyclohex-2-enyloxy)-acetic acid

Product 1

HCID 102723501-[(3-Chloro-4-methanesulfonyl-phenyl)-(cyclohex-2-enyloxy)-acetyl]-3-methyl-ureaYield 54.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A cooled (0° C.) mixture of rac-(3-chloro-4-methanesulfonyl-phenyl)-(cyclohex-2-enyloxy)-acetic acid (from Example 8100 mg, 0.29 mmol), fluorobenzene (2.5 mL) and N,N-dimethylformamide (1.8 μL). was treated with a 2.0 M solution of oxalyl chloride in dichloromethane (0.18 mL, 0.36 mmol) which caused a vigorous evolution of gas. The reaction was then stirred at 25° C. for 1 h and became light yellow in color. After methyl urea (64 mg, 0.87 mmol) was added, the reaction was heated at 70° C. for 10 min, then pyridine (0.048 mL, 0.60 mmol) was added and the mixture was maintained at 70° C. for 1 h. The cooled reaction was diluted with ethyl acetate (5 mL), then was filtered through celite to remove insoluble materials and the filtrate was concentrated in vacuo. The concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL), and brine (1×15 mL), then was dried over sodium sulfate, filtered and evaporated under reduced pressure. The reaction product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate) to give 1-[(3-chloro-4-methanesulfonyl-phenyl)-(cyclohex-2-enyloxy)-acetyl]-3-methyl-urea (63 mg, 54% yield) as a white foam: FAB-HRMS m/e calculated for C17H21N2O5SCl (M+H)+ 401.0938, found 401.0921.

Workup

  1. temperatureA cooled
  2. temperaturethe reaction was heated at 70° C. for 10 min
  3. temperaturethe mixture was maintained at 70° C. for 1 h
  4. customThe cooled reaction
  5. filtrationwas filtered through celite
  6. customto remove insoluble materials
  7. concentrationthe filtrate was concentrated in vacuo
  8. washThe concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL), and brine (1×15 mL)
  9. dry with materialwas dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe reaction product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6e06c4350e6944f4bb6396c6c8db22e4
Source dataset
uspto-grants-2003_08
Patent number
US06608218B2

Reaction notes

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