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

HRID 1953213Notes

Reaction equation

HRID 1953213 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>ClCCl>[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

7

Reactant 5

HCID 313Hydrochloric AcidHCID 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 6344DichloromethaneSolvent

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. The mixture was allowed to warm to ambient temperature overnight. This mixture was then 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 dichloromethane, prepared as described above, without isolation, causing an exotherm to about 8° C. This mixture was stirred at 0° C. for 30 minutes and at ambient temperature for about one hour. The reaction was then treated with 50 mL of 2N aqueous hydrochloric acid and was stirred 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)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester in dichloromethane was used for the preparation of 3-[[4-(4-fluorophenoxy)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid without isolation. An aliquot was concentrated to a foam.

Workup

  1. customto precipitate
  2. temperatureThis mixture was then cooled to 0° C.
  3. customprepared
  4. customto about 8° C
  5. stirringwas stirred 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)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid ethyl ester in dichloromethane was used for the preparation of 3-[[4-(4-fluorophenoxy)benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl)amino]propionic acid without isolation
  9. concentrationAn aliquot was concentrated to a foam

Sources & evidence

ORD record
ord-6ca4832afcd7418dadeb5aaff6a164b2
Source dataset
uspto-grants-2000_09
Patent number
US06114568

Reaction notes

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