Hydroxyamine hydrochloride → 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde oxime

HRID 1517611Notes

Reaction equation

HRID 1517611 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:28][CH2:29][C:30]([F:32])([F:31])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:27])=[N:16][N:17]([C:19]2[C:24]([CH:25]=O)=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:9][CH2:8]3.Cl.[NH2:34][OH:35].C([O-])(=O)C.[Na+]>C(O)C>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:28][CH2:29][C:30]([F:31])([F:32])[C:4]=2[CH:3]=1)[CH2:8][CH2:9][N:10]([CH2:13][C:14]1[C:15]([CH3:27])=[N:16][N:17]([C:19]2[C:24]([CH:25]=[N:34][OH:35])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:11][CH2:12]3

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 582685962-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde

Product 1

HCID 767507082-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde oximeYield 50.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde (0.210 g, 0.438 mmol) in ethanol (3 mL) are added hydroxylamine hydrochloride (0.038 g, 0.526 mmol) and sodium ethanoate (0.044 g, 0.526 mmol) and the mixture is stirred at reflux for 1 h. The solvent is evaporated and the residue is extracted with ethyl acetate and water. The organic layer is separated, dried over magnesium sulfate, filtered and the solvent is evaporated in vacuo. The residue is purified by basic reverse phase HPLC to yield 0.110 g of 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde oxime. MS (m/z): 494 (M+1).

Workup

  1. temperatureat reflux for 1 h
  2. customThe solvent is evaporated
  3. extractionthe residue is extracted with ethyl acetate and water
  4. customThe organic layer is separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent is evaporated in vacuo
  8. customThe residue is purified by basic reverse phase HPLC

Sources & evidence

ORD record
ord-b1196ebb46a94370ac4d318573dab979
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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