Dimethylformamide → N-hydroxy-2-(R)-{[4-(5-chloropyridin-2-yl-oxy)piperidine-1-sulfonyl]amino}-3-methylbutyramide

HRID 1856871Notes

Reaction equation

HRID 1856871 reaction equation
C(Cl)(=O)C(Cl)=O.CN(C=O)C.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([S:26]([NH:29][C@H:30]([CH:34]([CH3:36])[CH3:35])[C:31]([OH:33])=O)(=[O:28])=[O:27])[CH2:22][CH2:21]2)=[N:17][CH:18]=1.C[Si](C)(C)[NH:39][O:40][Si](C)(C)C>C(Cl)Cl>[OH:40][NH:39][C:31](=[O:33])[C@H:30]([NH:29][S:26]([N:23]1[CH2:22][CH2:21][CH:20]([O:19][C:16]2[CH:15]=[CH:14][C:13]([Cl:12])=[CH:18][N:17]=2)[CH2:25][CH2:24]1)(=[O:28])=[O:27])[CH:34]([CH3:35])[CH3:36]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 898151,1,1-trimethyl-N-((trimethylsilyl)oxy)silylamineHCID 187271352-(R)-{[4-(5-chloropyridin-2-yloxy)piperidine-1-sulfonyl]amino}-3-methylbutyric acid

Product 1

HCID 10069936N-hydroxy-2-(R)-{[4-(5-chloropyridin-2-yl-oxy)piperidine-1-sulfonyl]amino}-3-methylbutyramideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.58 ml, 6.7 mmol) and DMF (few drops) were added to a solution of (R)-2-{[4-(5-chloropyridin-2-yloxy)piperidine-1sulfonyl)amino}-3-methylbutyric acid (1.05 g, 2.7 mmol), [prepared as described in Step 1 above], in methylene chloride (85 ml) and the reaction mixture was stirred overnight at RT. After removal of the organics, the residue was redissolved in methylene chloride (40 ml) and N,O-bis-trimethylsilylhydroxylamine (1.7 g, 9.4 mmol) was added. After 3 h, the reaction was concentrated, methanol (20 ml) was added and after stirring for an additional 30 min., the solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine, dried over MgSO4, and concentrated. Chromatography (SiO2, 1-2% methanol/methylene chloride) gave N-hydroxy-2-(R)-{[4-(5-chloropyridin-2-yl-oxy)piperidine-1-sulfonyl]amino}-3-methylbutyramide as a white solid (35%), mp 97.0-98.4° C.

Workup

  1. customAfter removal of the organics, the residue
  2. dissolutionwas redissolved in methylene chloride (40 ml)
  3. waitAfter 3 h
  4. concentrationthe reaction was concentrated
  5. additionmethanol (20 ml) was added
  6. stirringafter stirring for an additional 30 min.
  7. customthe solvent was removed in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. washwashed with water and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-ff779d3dd93a4c2b95d33bb56b68096f
Source dataset
uspto-grants-2000_11
Patent number
US06143744

Reaction notes

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