Hydroxylamine → HCID 22615616, compound

HRID 843017Notes

Reaction equation

HRID 843017 reaction equation
[OH:1][N:2]1C(=O)CCC1=O.Cl.CN(C)CCCN=C=NCC.[OH:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][CH:26]=[C:25]2[CH:31]1[CH2:36][CH2:35][N:34]([S:37]([N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH:41]2[C:46](O)=[O:47])(=[O:39])=[O:38])[CH2:33][CH2:32]1.NO>CN(C)C1C=CN=CC=1.CN(C)C=O.C(Cl)Cl.C(Cl)Cl.CO>[OH:1][NH:2][C:46]([CH:41]1[CH2:42][CH2:43][CH2:44][CH2:45][N:40]1[S:37]([N:34]1[CH2:33][CH2:32][CH:31]([C:25]2[C:24]3[C:28](=[CH:29][CH:30]=[C:22]([OH:21])[CH:23]=3)[NH:27][CH:26]=2)[CH2:36][CH2:35]1)(=[O:39])=[O:38])=[O:47]

Participants

9

Reactant 4

HCID 787HydroxylamineHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22615659HCID 22615659, compound

Product 1

HCID 22615616HCID 22615616, compoundYield 22%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

N-Hydroxysuccinimide (0.181 g, 1.57 mmol), 4-dimethylaminopyridine (96 mg, 0.78 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.33 g, 1.73 mmol) were added to a solution of 1-[4-(5-hydroxyindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(RS)-carboxylic acid (0.32 g, 0.78 mmol) [prepared as described in Step 2 above] in 30% dimethylformamide/methylene chloride (5.5 ml). After stirring at RT for 2 h, the reaction was diluted with methylene chloride (50 ml) and washed with 1M HCl, brine and dried over MgSO4. The organics were evaporated in vacuo and the residue was dissolved in 50% ethyl acetate/methanol (13.4 ml). This solution was added to a solution of 50% aqueous hydroxylamine (6.7 ml, 109 mmol) in methanol (6.7 ml) at −30° C. with vigorous stirring. After 10 min., the reaction mixture was quenched with 1M HCl (final pH=3) and then concentrated in vacuo. The residue was extracted with ethyl acetate and the organic layer was washed with brine and dried over MgSO4. The organics were evaporated in vacuo and the residue was chromatographed (SiO2, 10% methanol/methylene chloride) to give N-hydroxy-1-[4-(5-hydroxyindol-3-yl)piperidine-1-sulfonyl]piperidine-2-(RS)-carboxamide (22%) as a white solid.

Workup

  1. washwashed with 1M HCl, brine
  2. dry with materialdried over MgSO4
  3. customThe organics were evaporated in vacuo
  4. dissolutionthe residue was dissolved in 50% ethyl acetate/methanol (13.4 ml)
  5. waitAfter 10 min.
  6. customthe reaction mixture was quenched with 1M HCl (final pH=3) and
  7. concentrationthen concentrated in vacuo
  8. extractionThe residue was extracted with ethyl acetate
  9. washthe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. customThe organics were evaporated in vacuo
  12. customthe residue was chromatographed (SiO2, 10% methanol/methylene chloride)

Sources & evidence

ORD record
ord-93fd775050834238a721ebf7f7295e36
Source dataset
uspto-grants-2002_04
Patent number
US06376506B1

Reaction notes

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