Water → HCID 10387699, compound

HRID 1601248Notes

Reaction equation

HRID 1601248 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 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of sodium hydride (0.37 g, 7 mmol of a 50% oil dispersion) in dimethylformiamide (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 pare 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-3c210eb6fb9344b98f8d943096b0f5d3
Source dataset
uspto-grants-1999_11
Patent number
US05977113

Reaction notes

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