Hydrazine hydrate (1:1) → N1-[4-(2-Benzyloxy-4-ethylphenoxy)-3-fluorophenyl]propan-1,3-diamine

HRID 626069Notes

Reaction equation

HRID 626069 reaction equation
[CH2:1]([O:8][C:9]1[CH:23]=[C:22]([CH2:24][CH3:25])[CH:21]=[CH:20][C:10]=1[O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[F:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrCCCC1C=CC=[C:32]2[C:33]([NH:35]C(=O)[C:31]=12)=O.O.NN>C(O)C.C(OC(=O)C)C>[CH2:1]([O:8][C:9]1[CH:23]=[C:22]([CH2:24][CH3:25])[CH:21]=[CH:20][C:10]=1[O:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][CH2:31][CH2:32][CH2:33][NH2:35])=[CH:14][C:13]=1[F:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 21958088BromopropylphthalimideHCID 591912224-(2-Benzyloxy-4-ethylphenoxy)-3-fluoroaniline

Product 1

HCID 59191220N1-[4-(2-Benzyloxy-4-ethylphenoxy)-3-fluorophenyl]propan-1,3-diamineYield 18.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To 4-(2-benzyloxy-4-ethylphenoxy)-3-fluoroaniline (500 mg, 1.48 mmol) in 25 ml of ethanol was added 3-bromopropylphthalimide (440 mg, 1.64 mmol). The mixture was refluxed for 2 days. The reaction mixture was diluted with ethylacetate and washed with water, saturated brine solution, dried over anhydrous Na2SO4 and concentrated. The crude obtained was passed through a silica gel column using 15% ethylacetate in petroleum ether as eluant. The LCMS of the obtained mixture showed 53% mass of the coupled product. This was taken in 25 ml of ethanol and added 7 ml of hydrazine hydrate and refluxed overnight. Ethanol was removed in vacuo and added 20% KOH solution (20 ml) to the residue. The aqueous fraction was then extracted with dichlormethane and the combined dichloromethane fraction was dried over anhydrous Na2SO4 and concentrated. The crude product obtained was purified by column chromatography using 5% methanol in dichloromethane as eluant to obtain 110 mg (18.8% after 2 steps) of the N1-[4-(2-Benzyloxy-4-ethylphenoxy)-3-fluorophenyl]propan-1,3-diamine.

Workup

  1. temperatureThe mixture was refluxed for 2 days
  2. washwashed with water, saturated brine solution
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe crude obtained
  6. temperaturerefluxed overnight
  7. customEthanol was removed in vacuo
  8. additionadded 20% KOH solution (20 ml) to the residue
  9. extractionThe aqueous fraction was then extracted with dichlormethane
  10. dry with materialthe combined dichloromethane fraction was dried over anhydrous Na2SO4
  11. concentrationconcentrated
  12. customThe crude product obtained
  13. customwas purified by column chromatography

Sources & evidence

ORD record
ord-fe026a3fa09d4073872d52159b33baac
Source dataset
uspto-grants-2016_04
Patent number
US09309179B2

Reaction notes

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