Pyridine → Rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea

HRID 397196Notes

Reaction equation

HRID 397196 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.ClCCl.[CH3:31][NH:32][C:33]([NH2:35])=[O:34].N1C=CC=CC=1>FC1C=CC=CC=1.CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:35][C:33]([NH:32][CH3:31])=[O:34])=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

9

Reactant 5

HCID 1049PyridineHCID 6344DichloromethaneHCID 11719MethylureaHCID 65578Oxalyl chlorideHCID 18172604Rac-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetic acid

Product 1

HCID 10200321Rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-ureaYield 67%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 10008FluorobenzeneSolvent

Conditions

Temperature
25 °C

Procedure

A cooled (0° C.) solution of rac-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetic acid (Example 6; 100 mg, 0.30 mmol) in 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). Immediately a vigorous gas evolution was observed, and the mixture was stirred at 25° C. for 1 h and became light yellow in color. Methyl urea (97 mg, 0.90 mmol) was then added and after the reaction was heated at 70° C. for 10 min, pyridine (0.048 mL, 0.60 mmol) was added and the reaction was maintained at 70° C. for 1 h. The cooled mixture was diluted with ethyl acetate (5 mL) then was filtered through Celite to remove insoluble materials and the filtrate 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 product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate) to provide rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea (78 mg, 67% yield) as a white foam: FAB-HRMS m/e calculated for C16H21N2O5SCl (M+H)+ 389.0938, found 389.0943.

Workup

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

Sources & evidence

ORD record
ord-6656c40ae0bc47fc9cc442e755907f4b
Source dataset
uspto-grants-2003_08
Patent number
US06608218B2

Reaction notes

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