Sodium hydride → 5-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamide

HRID 4797Notes

Reaction equation

HRID 4797 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([OH:13])=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10].CS(O[CH:19]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]1)(=O)=O>CN(C)C=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:13][CH:19]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20]2)=[C:8]([CH:12]=1)[C:9]([NH2:11])=[O:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 137262825-Fluoro-2-hydroxybenzamideHCID 219142741-Methylpyrrolidin-3-yl methanesulfonate

Product 1

HCID 137262885-Fluoro-2-(1-methyl-3-pyrrolidinyloxy)benzamideYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of 0.44 g (60% in oil, 0.011 mole) of sodium hydride in 10 ml of dimethylformamide was added 1.55 g (0.01 mole) of 5-fluoro-2-hydroxybenzamide in 10 ml of dimethylformamide under nitrogen atmosphere at room temperature. The reaction mixture was heated to 60° C. and 1.80 g (0.01 mole) of 1-methyl-3-pyrrolidinol methane sulfonate (ester) was added. The reaction mixture was then heated to 100° C. for 18 hr. The dimethylformamide was removed by rotary evaporation at 70° C., 0.5 mm Hg. The residue was taken up in 200 ml of methylene chloride, washed with 2×50 ml of 1N sodium hydroxide and 50 ml of water. The organic phase was extracted with 2×50 ml of 1N hydrochloric acid. The combined aqueous extracts were washed with 50 ml of methylene chloride, made basic with concentrated sodium hydroxide and extracted into 2×50 ml of methylene chloride. The combined organic extracts were dried over sodium sulfate, filtered and concentrated by rotary evaporation. The residual oil was crystallized from hexane to give 1.0 g of off-white crystals. m.p. 90°-93° C.

Workup

  1. temperatureThe reaction mixture was then heated to 100° C. for 18 hr
  2. customThe dimethylformamide was removed by rotary evaporation at 70° C.
  3. washwashed with 2×50 ml of 1N sodium hydroxide and 50 ml of water
  4. extractionThe organic phase was extracted with 2×50 ml of 1N hydrochloric acid
  5. washThe combined aqueous extracts were washed with 50 ml of methylene chloride
  6. extractionextracted into 2×50 ml of methylene chloride
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe residual oil was crystallized from hexane

Sources & evidence

ORD record
ord-997cc09958b640a1bde80518045ba4ee
Source dataset
uspto-grants-1988_02
Patent number
US04727152

Reaction notes

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