Pyridine → 3-[[4-(4-Fluorophenoxy)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester

HRID 1596007Notes

Reaction equation

HRID 1596007 reaction equation
Cl.[NH2:2][OH:3].N1C=CC=CC=1.C[Si](Cl)(C)C.[CH2:15]([O:17][C:18](=[O:47])[CH2:19][CH2:20][N:21]([C:39]1([C:44](Cl)=[O:45])[CH2:43][CH2:42][CH2:41][CH2:40]1)[S:22]([C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)=[CH:27][CH:26]=1)(=[O:24])=[O:23])[CH3:16]>Cl>[CH2:15]([O:17][C:18](=[O:47])[CH2:19][CH2:20][N:21]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:39]1([C:44](=[O:45])[NH:2][OH:3])[CH2:43][CH2:42][CH2:41][CH2:40]1)[CH3:16]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 443297Hydroxyamine hydrochlorideHCID 154912553-{(1-Chlorocarbonylcyclopentyl)-[4-(4-fluorophenoxy)benzenesulfonyl]amino}propionic acid ethyl ester

Product 1

HCID 98057753-[[4-(4-Fluorophenoxy)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution of 1.37 g (19.7 mmol, 1.3 equivalents) of hydroxylamine hydrochloride in 9.2 mL (114 mmol, 7.5 equivalents) of dry pyridine at 0° C. was treated with 5.8 mL (45 mmol, 3.0 equivalents) of trimethylsilyl chloride, causing white solids to precipitate, and allowedc to warm to ambient temperature overnight. This mixture was cooled to 0° C. and treated with a solution of 7.54 g (15.1 mmol) of 3-{(1-chlorocarbonylcyclopentyl)-[4-(4-fluorophenoxy)benzenesulfonyl]amino}propionic acid ethyl ester in 73 mL of dichloromethene, prepared as described above without isolation, causing an exotherm to 8° C. This mixture was stirred at 0° C. for 30 minutes and at ambient temperature for one hour before treating with 50 mL of 2N aqueous hydrochloric acid and stirring at ambient temperature for one hour. The aqueous phase was extracted with dichloromethane and the combined organic phases were washed with 2N aqueous hydrochloric acid (2×50 mL) and water (50 mL). This solution of 3-[[4-(4-fluorophenoxy)benzenesufonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester in dichloromethane was used for the preparation of 3-[[4-(4-fluoro-phenoxy)benzenesulfonyl]-1-hydroxycarbamoylcyclopentyl)amino]propionic acid without isolation. An aliquot was concentrated to a foam.

Workup

  1. customto precipitate
  2. temperatureThis mixture was cooled to 0° C.
  3. customprepared
  4. customto 8° C
  5. stirringstirring at ambient temperature for one hour
  6. extractionThe aqueous phase was extracted with dichloromethane
  7. washthe combined organic phases were washed with 2N aqueous hydrochloric acid (2×50 mL) and water (50 mL)
  8. customThis solution of 3-[[4-(4-fluorophenoxy)benzenesufonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester in dichloromethane was used for the preparation of 3-[[4-(4-fluoro-phenoxy)benzenesulfonyl]-1-hydroxycarbamoylcyclopentyl)amino]propionic acid without isolation
  9. concentrationAn aliquot was concentrated to a foam

Sources & evidence

ORD record
ord-12af4764d7db4e399f2ca34ca2d22f36
Source dataset
uspto-grants-2001_09
Patent number
US06288246B1

Reaction notes

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