Triphenylphosphine → 4-{2-[4-(3,6-Dichloro-pyridazin-4-yl)-piperazin-1-yl]ethoxy}-phenylacetic acid methyl ester

HRID 1958083Notes

Reaction equation

HRID 1958083 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5]([Cl:17])=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1.[CH2:18]([O:20][C:21](=[O:29])[C:22]1[CH:27]=[CH:26][C:25](O)=NC=1)C.[C:30]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:35]=CC=C[CH:31]=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:18][O:20][C:21](=[O:29])[CH2:22][C:27]1[CH:26]=[CH:25][C:35]([O:16][CH2:15][CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:7]3[CH:6]=[C:5]([Cl:17])[N:4]=[N:3][C:2]=3[Cl:1])[CH2:13][CH2:12]2)=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 817655582-[4-(3,6-Dichloropyridazin-4-yl)-piperazin-1-yl]-ethanolHCID 178469094HCID 178469094, compound

Product 1

HCID 159847264-{2-[4-(3,6-Dichloro-pyridazin-4-yl)-piperazin-1-yl]ethoxy}-phenylacetic acid methyl esterYield 42.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 50 mL dry three-necked flask, 0.554 g (0.002 mol) of self-made 2-[4-(3,6-dichloro-pyridazin-4-yl)-piperazin-1-yl]-ethanol, 0.28 g (0.002 mol) of 6-hydroxy-nicotinic acid ethyl ester, 0.612 g of triphenylphosphine were added, 15 mL of anhydrous tetrahydrofuran was poured into the flask under condition of ice bath and nitrogen gas protection, then 0.35 mL of diethyl azodiformate (DEAD) dissolved in 5 mL of anhydrous tetrahydrofuran was added dropwise into the flask, after the dropwise addition, the temperature was elevated to room temperature, the agitation was kept overnight. The solvent was removed by evaporation using a rotation evaporator next day, the residue was poured into 100 mL of water, extracted for three times using total 150 mL of dichloromethane, the extract solutions were combined together, dried over anhydrous Na2SO4, concentrated, and separated by column chromatograph (eluent, petroleum ether:ethyl acetate:methanol=10:5:0.15) to obtain 0.32 g of 4-{2-[4-(3,6-dichloro-pyridazin-4-yl)-piperazin-1-yl]ethoxy}-phenylacetic acid methyl ester, a white solid. Yield: 42.3%, m.p. 140˜141° C. 1H-NMR(400 MHz, CDCl3) δppm: 1.37˜1.41(t, 3H, J=7.3 Hz), 2.79(brs, 4H), 2.91(brs, 2H), 3.36(brs, 4H), 4.35˜4.40(q, 2H, J=7.3 Hz), 4.57(brs, 2H), 6.78˜6.80(d, 2H, J=8.7 Hz), 6.86(s, 1H), 8.16˜8.18(dd, 1H, J1=8.7 Hz, J2=2.2 Hz).

Workup

  1. additionwas added dropwise into the flask
  2. additionafter the dropwise addition
  3. customwas elevated to room temperature
  4. customThe solvent was removed by evaporation
  5. customa rotation evaporator next day
  6. additionthe residue was poured into 100 mL of water
  7. extractionextracted for three times
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customseparated by column chromatograph (eluent, petroleum ether:ethyl acetate:methanol=10:5:0.15)

Sources & evidence

ORD record
ord-dba2c739b92c4436b185870f0f497b80
Source dataset
uspto-grants-2013_04
Patent number
US08410105B2

Reaction notes

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