Hydrochloric Acid → tert-butyl 4-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]piperidine-1-carboxylate

HRID 1821888Notes

Reaction equation

HRID 1821888 reaction equation
[C:1]1([C:7]([C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:18][O:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.Cl>CCO.C(OCC)C>[C:1]1([C:7](=[N:18][O:19][CH:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]2)[C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 24729482tert-Butyl 4-(aminooxy)piperidine-1-carboxylateHCID 57893467HCID 57893467, compound

Product 1

HCID 136386509tert-butyl 4-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]piperidine-1-carboxylateYield 23%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone (Example 35) (300 mg, 1.34 mmol) and tert-butyl 4-(aminooxy)piperidine-1-carboxylate (Reference Example 10) (289 mg, 1.34 mmol) in EtOH (30 mL) was adjusted to pH 4-5 with HCl (1.9 mL of a 1 N HCl solution in diethyl ether, 1.9 mmol). The reaction mixture was heated to reflux. After 3 h, the reaction mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and saturated NaHCO3. The aqueous layer was separated and extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by column chromatography (silica gel, 98:2 CH2Cl2/MeOH to 95:5 CH2Cl2/MeOH) gave tert-butyl 4-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]piperidine-1-carboxylate (120 mg, 23%) as a white amorphous solid (geometry of the oxime double bond undefined).

Workup

  1. temperatureThe reaction mixture was heated to reflux
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe residue was partitioned between EtOAc and saturated NaHCO3
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by column chromatography (silica gel, 98:2 CH2Cl2/MeOH to 95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-14927dddd6514be5be5068a8e84905da
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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