Water → HCID 10387699, compound

HRID 1899516Notes

Reaction equation

HRID 1899516 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:32]=[CH:31][C:7]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][NH:20][C:21]4[CH:26]=[CH:25][C:24]([C:27](=[O:29])[CH3:28])=[CH:23][C:22]=4[OH:30])[CH2:13][CH2:12]3)=[N:9][O:10][C:6]=2[CH:5]=1.[CH3:33]I.O>CN(C)C=O>[F:3][C:4]1[CH:32]=[CH:31][C:7]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][NH:20][C:21]4[CH:26]=[CH:25][C:24]([C:27](=[O:29])[CH3:28])=[CH:23][C:22]=4[O:30][CH3:33])[CH2:13][CH2:12]3)=[N:9][O:10][C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10024607HCID 10024607, compound

Product 1

HCID 10387699HCID 10387699, compoundYield 164.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a stirred suspension of sodium hydride (0.37 g, 7 mmol of a 50% oil dispersion) in dimethylformamide (20 ml) was added, dropwise, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propylamino]-3-hydroxyphenyl]ethanone (2.9 g, 7 mmol) dissolved in dimethylformamide (25 ml). The reaction was stirred at ambient temperature for 15 minutes, and then it was cooled with an ice bath to about 5° C., whereupon methyl iodide (1.0 g, 7 mmol) in dimethylformamide (1 ml) was added dropwise. The reaction was stirred at ambient temperature for 30 min, and then water was added. The resulting aqueous mixture was extracted with ethyl acetate, the extract washed with water, dried (MgSO4), and the solvent was concentrated to afford 4.9 g of a brown oil, which solidified on standing. The solid was flash chromatographed on silica gel. The appropriate fractions were concentrated to yield 2.7 g of product as a yellow solid. Recrystallization from toluene-hexane yielded 2.0 g (67%) of analytically pure 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propylaminol-3-methoxyphenyl]ethanone as a yellow solid, m.p.=96°-98° C.

Workup

  1. additionwas added
  2. additionwas added dropwise
  3. stirringThe reaction was stirred at ambient temperature for 30 min
  4. extractionThe resulting aqueous mixture was extracted with ethyl acetate
  5. washthe extract washed with water
  6. dry with materialdried (MgSO4)
  7. concentrationthe solvent was concentrated

Sources & evidence

ORD record
ord-ce22df22084042469c4ff8741b9b8748
Source dataset
uspto-grants-1996_11
Patent number
US05571828

Reaction notes

Loading…