Potassium Iodide → HCID 22824882, compound

HRID 904836Notes

Reaction equation

HRID 904836 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5]1[C:9]2[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:8]=2[O:7][N:6]=1.[C:15](=[O:18])([O-])[O-].[K+].[K+].[I-].[K+].[CH3:23][N:24]([CH3:27])C=O>>[ClH:1].[F:14][C:12]1[CH:11]=[CH:10][C:9]2[C:5]([CH2:4][CH2:3][CH2:2][N:24]3[CH2:27][CH2:11][CH2:12][C@@:13]4([CH2:8][C@@H:9]5[CH2:5][CH:4]=[CH:3][CH:2]=[C:15]5[O:18]4)[CH2:23]3)=[N:6][O:7][C:8]=2[CH:13]=1

Participants

5

Reactant 4

HCID 4875Potassium IodideHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 109108803-(3-Chloropropyl)-6-fluorobenzo[d]isoxazole

Product 1

HCID 22824882HCID 22824882, compoundYield 38%

Conditions

Temperature
90 °C

Procedure

In 50 ml dry dimethylformamide (DMF) were combined 5.00 g (22.2 mmol) 2,3-dihydro-spiro[benzofuran-2(3H),3'-piperidine]hydrochloride of Example 1c, 7.41 g (1.25 equivalents) 3-(3-chloropropyl)-6-fluoro-1,2-benzisoxazole of Example 1d, 18.4 g (6 equivalents) milled anhydrous potassium carbonate, and a catalytic amount (0.5 g) potassium iodide. The mixture was stirred under nitrogen at 90° C. for three and one-half hours, then cooled and filtered. The DMF was evaporated in vacuo to an oil which was partitioned between 10% K2CO3 and ether. The ether was separated, washed with water, saturated aqueous alt solution, dried over MgSO4, filtered, and passed through a column of 40 g alumina in ether. The product-containing fractions were combined and adjusted to pH 1 with ethereal-HCl. The resultant precipitate was collected and recrystallized from 1:1 dichloromethane/ethyl acetate to yield 3.36 g (38%) of (R,S)-dihydro-1'-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-spiro[benzofuran-2(3H),3'-piperidine]hydrochloride, m.p. 257°-259° C.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. customThe DMF was evaporated in vacuo to an oil which
  4. customwas partitioned between 10% K2CO3 and ether
  5. customThe ether was separated
  6. washwashed with water, saturated aqueous alt solution
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customThe resultant precipitate was collected
  10. customrecrystallized from 1:1 dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-7f8975b728794ae8a4783842ea45b888
Source dataset
uspto-grants-1983_12
Patent number
US04420485

Reaction notes

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