Water → HCID 68842884, compound

HRID 2274403Notes

Reaction equation

HRID 2274403 reaction equation
[H-].[Na+].[N:3]1([CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[F:14][C:15]1[C:21](F)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1.O>CN(C=O)C>[F:14][C:15]1[C:21]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][N:3]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1571514,5-Difluoro-2-nitroanilineHCID 4189434-(Piperidin-1-yl)butan-1-ol

Product 1

HCID 68842884HCID 68842884, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

382 mg of sodium hydride (60% in suspension in oil) are added in small portions, over two hours, to a solution of 4-piperidin-1-ylbutan-1-ol in 10 mL of DMF, cooled to 0° C. with an ice bath. A solution of 4,5-difluoro-2-nitroaniline in 5 mL of N,N-dimethylformamide is then added dropwise. The medium is stirred at ambient temperature for 24 hours. 60 mL of distilled water are added and the reaction medium is extracted with 3×30 mL of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on an Intelliflash apparatus with an Analogix RS-12 silica cartridge, with a 100% to 85/15 dichloromethane/-methanol elution gradient. 700 mg of 4-fluoro-2-nitro-5-(4-piperidin-1-ylbutoxy)phenylamine are isolated in the form of a red oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): from 1.29 to 1.62 (m, 8H); 1.75 (m, 2H); 2.28 (m, 6H); 4.07 (t, J=6.5 Hz, 2H); 6.62 (d, J=7.5 Hz, 1H); 7.48 (broad s, 2H); 7.74 (d, J=12.0 Hz, 1H).

Workup

  1. extractionthe reaction medium is extracted with 3×30 mL of ethyl acetate
  2. dry with materialThe combined organic phases are dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum in a rotary evaporator
  5. customThe reaction crude
  6. customis purified by flash chromatography on an Intelliflash apparatus with an Analogix RS-12 silica cartridge, with a 100% to 85/15 dichloromethane/-methanol elution gradient

Sources & evidence

ORD record
ord-3c5996aba5814dd7a7bedee3c873aabf
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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