Pyrrolidine → HCID 136463725, compound

HRID 862107Notes

Reaction equation

HRID 862107 reaction equation
[Cl:1][C:2]1[C:3]([F:22])=[CH:4][C:5]([OH:21])=[C:6]([CH:20]=1)[C:7]([C:9]1[C:14]([CH:15]2[O:19][CH2:18][CH2:17][O:16]2)=[CH:13][CH:12]=[CH:11][N:10]=1)=O.Cl.[C:24]([O:28][NH2:29])([CH3:27])([CH3:26])[CH3:25].N1CCCC1>C(O)CC>[C:24]([O:28]/[N:29]=[C:7](\[C:9]1[C:14]([CH:15]2[O:19][CH2:18][CH2:17][O:16]2)=[CH:13][CH:12]=[CH:11][N:10]=1)/[C:6]1[CH:20]=[C:2]([Cl:1])[C:3]([F:22])=[CH:4][C:5]=1[OH:21])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 2777906O-tert-butylhydroxylamine hydrochlorideHCID 19701602HCID 19701602, compound

Product 1

HCID 136463725HCID 136463725, compoundYield 30.5%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Procedure

A solution of 2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine (1.45 g), O-t-butylhydroxylamine hydrochloride (1.69 g) and pyrrolidine (9.56 g) in n-propanol (20 ml) was heated for 1.5 hour under reflux. The reaction mixture was concentrated, to which was added water, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give a mixture (540 mg) of (Z)-2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine O-t-butyloxime and (Z)-2-[5-chloro-2-hydroxy-4-(pyrrolidin-1-yl)benzoyl]-3-(1,3-dioxolan-2-yl)pyridine O-t-butyloxime (about 2:1). A mixture of this mixture (470 mg), p-toluenesulfonic acid monohydrate (162 mg), acetone (9.0 ml) and water (3.5 ml) was heated for 14 hours under reflux. The reaction mixture was concentrated, to which was added water, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated to leave an oily substance. This oily substance was dissolved in chloroform (2.0 ml), to which was added, at room temperature, 50% m-chloroperbenzoic acid (75 mg). The mixture was stirred for 8 minutes at the same temperature, which was then poured into an aqueous solution of sodium sulfite, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give (Z)-2-(5-chloro-4-fluoro-2-hydroxybenzoyl)-3-formylpyridine O-t-butyloxime (230 mg) (Compound 155).

Workup

  1. temperatureunder reflux
  2. concentrationThe reaction mixture was concentrated, to which
  3. additionwas added water
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe extract solution was washed with a saturated aqueous saline solution
  6. dry with materialdried (anhydrous sodium sulfate)
  7. concentrationconcentrated
  8. customThe concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane)

Sources & evidence

ORD record
ord-58bf8086aa034b488bb2662ee239bd38
Source dataset
uspto-grants-1998_02
Patent number
US05716971

Reaction notes

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