Methanol → 4-(6-Chloro-1,2-benzisoxazol-3-yl)-1-piperidinecarboxaldehyde

HRID 2417714Notes

Reaction equation

HRID 2417714 reaction equation
[H-].[Na+].C([O:5][N:6]=[C:7]([CH:16]1[CH2:21][CH2:20][N:19]([CH:22]=[O:23])[CH2:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1Cl)=O.CO.[Cl-].[Na+]>O1CCCC1.CN(C)C=O.O>[CH:22]([N:19]1[CH2:20][CH2:21][CH:16]([C:7]2[C:8]3[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=3[O:5][N:6]=2)[CH2:17][CH2:18]1)=[O:23]

Participants

8

Reactant 4

HCID 887MethanolHCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 86738605HCID 86738605, compound

Product 1

HCID 130764214-(6-Chloro-1,2-benzisoxazol-3-yl)-1-piperidinecarboxaldehydeYield 80.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of 1.25 g of sodium hydride (prepared from 2.5 g 50% oil dispersion) in 100 ml of tetrahydrofuran was added, over 20 mins, a solution of 10 g of 1-formyl-4-(2,4-dichlorobenzoyl)piperidine O-formyl oxime in 60 ml of dimethylformamide and 40 ml of tetrahydrofuran. The stirred mixture was heated to 80°-90° (oil bath temperature) for 5 hrs and after standing at 20° for 16 hrs, 10 ml of methanol and 20 ml of water were added. The reaction mixture was added to about 1.2 l of saturated sodium chloride solution. The mixture was extracted with 400 ml of ether. The extract was washed with 800 ml of water. The aqueous phase was extracted with 400 ml of ether and the combined ether extracts were distilled to yield an oil, which crystallized on standing. Recrystallization from isopropanol-ether gave 6.5 g (67.2%) of product, mp 114°- 115°.

Workup

  1. additionwas added, over 20 mins
  2. temperatureThe stirred mixture was heated to 80°-90° (oil bath temperature) for 5 hrs
  3. extractionThe mixture was extracted with 400 ml of ether
  4. washThe extract was washed with 800 ml of water
  5. extractionThe aqueous phase was extracted with 400 ml of ether
  6. distillationthe combined ether extracts were distilled
  7. customto yield an oil, which
  8. customcrystallized
  9. customRecrystallization from isopropanol-ether

Sources & evidence

ORD record
ord-5718845c1b1e4d39bb4041904aa5ba5c
Source dataset
uspto-grants-1984_09
Patent number
US04469869

Reaction notes

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