Sodium hydride → 4-Fluoro-2-nitro-5-(3-piperidin-1-ylpropoxy)phenylamine

HRID 2274394Notes

Reaction equation

HRID 2274394 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:13][C:14]1[C:19](F)=[CH:18][C:17]([NH2:21])=[C:16]([N+:22]([O-:24])=[O:23])[CH:15]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[F:13][C:14]1[C:19]([O:10][CH2:9][CH2:8][CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:18][C:17]([NH2:21])=[C:16]([N+:22]([O-:24])=[O:23])[CH:15]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 66032Piperidine-1-propanolHCID 1571514,5-Difluoro-2-nitroanilineHCID 516892Sodium Bicarbonate

Product 1

HCID 688437124-Fluoro-2-nitro-5-(3-piperidin-1-ylpropoxy)phenylamine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.3 mL of 3-piperidin-1-ylpropan-1-ol in 16 mL of N,N-dimethylformamide (DMF) is cooled to 0° C. with an ice bath. 345 mg of sodium hydride (60% in suspension in oil) are added in small portions. The suspension obtained is added dropwise to a suspension containing 500 mg of 4,5-difluoro-2-nitrophenylamine and 724 mg of sodium bicarbonate in 15 mL of DMF. The reaction medium is stirred for one hour at ambient temperature and then heated for 1 hour at 90° C. The cooled reaction medium is treated with 70 mL of ethyl acetate and 70 mL of distilled water. The aqueous phase is extracted with 70 mL of ethyl acetate. The combined organic phases are washed with 100 mL of distilled water and 100 mL of a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent is concentrated to dryness in a rotary evaporator and the crude is then purified by chromatography on a 50 g silica cartridge, eluent: 100/0 to 80/20 dichloromethane/methanol. 300 mg of 4-fluoro-2-nitro-5-(3-piperidin-1-ylpropoxy)phenylamine are isolated in the form of a yellow oil which crystallizes. Analytical LC/MS: Tr=2.26 min, [M+H]+=298.04 DAD=87%.

Workup

  1. customThe suspension obtained
  2. additionis added dropwise to a suspension
  3. temperatureheated for 1 hour at 90° C
  4. customThe cooled reaction medium
  5. extractionThe aqueous phase is extracted with 70 mL of ethyl acetate
  6. washThe combined organic phases are washed with 100 mL of distilled water and 100 mL of a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationThe solvent is concentrated to dryness in a rotary evaporator
  9. customthe crude is then purified by chromatography on a 50 g silica cartridge, eluent

Sources & evidence

ORD record
ord-c478d36d84034e15b212c1cf638a4e2b
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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