Hydrochloric Acid → N-hydroxy-2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionamide

HRID 609685Notes

Reaction equation

HRID 609685 reaction equation
[OH-:1].[K+].Cl.[NH2:4]O.[CH2:6]([N:13]([S:20]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1)(=[O:22])=[O:21])[C@H:14]([CH3:19])[C:15](OC)=[O:16])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.ClC1C=CC(OC2CCNCC2)=NC=1.ClC1C=CC(N2CCNCC2)=CC=1.Cl>CO.C(Cl)Cl>[OH:1][NH:4][C:15](=[O:16])[C@H:14]([N:13]([CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[S:20]([N:23]1[CH2:24][CH2:25][N:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[CH2:27][CH2:28]1)(=[O:22])=[O:21])[CH3:19]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 974781-(4-Chlorophenyl)piperazineHCID 443297Hydroxyamine hydrochlorideHCID 112643295-Chloro-2-(piperidin-4-yloxy)pyridineHCID 18727246methyl 2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionate

Product 1

HCID 18727267N-hydroxy-2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 6344DichloromethaneSolvent

Procedure

A solution of potassium hydroxide (1.6 g, 29.2 mmol) in methanol (9.8 ml) was added to a solution of hydroxylamine hydrochloride (1.02 g, 14.6 mmol) in methanol (9.8 ml) at 0° C. After 5 min., a solution of methyl 2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionate (1.101 g, 2.44 mmol) in methanol (9.8 ml), [prepared as described in Example 2, Step, 2, but replacing D-valinesulfamoyl chloride methyl ester and 4-(5-chloropyridin-2-yloxy)piperidine with D-alaninesulfamoyl chloride methyl ester and 4-(4-chlorophenyl)piperazine respectively, followed by benzylation as described in Example 4] was added and the reaction temperature was allowed to rise to RT. After 5 h, the reaction mixture was diluted with methylene chloride (147 ml) and neutralized with 10% aqueous HCl. The solvent was removed in vacuo and the residue was dissolved in methanol. The insoluble salts were filtered off and N-hydroxy-2-(R)-{benzyl-[4-(4-chlorophenyl)piperazine-1-sulfonyl]amino}-propionamide was isolated using reverse phase preparative HPLC (20-70% acetonitrile/0.1% aqueous trifluoroacetic acid) as a crystalline solid (23%).

Workup

  1. additionwas added
  2. customto rise to RT
  3. waitAfter 5 h
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in methanol
  6. filtrationThe insoluble salts were filtered off

Sources & evidence

ORD record
ord-baa475f806f84c31aef014300d8aa05b
Source dataset
uspto-grants-1999_12
Patent number
US05998412

Reaction notes

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