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

HRID 370894Notes

Reaction equation

HRID 370894 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-8fc5f03e91f24be3a8778a4efd5771df
Source dataset
uspto-grants-1985_07
Patent number
US04528376

Reaction notes

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