Ethanol → Ethyl 4-[2-[4-(4-pyridyl)piperazin-2-one-1-yl]acetyl]phenoxyacetate

HRID 2250Notes

Reaction equation

HRID 2250 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([C:16]3[CH:26]=[CH:25][C:19]([O:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:18][CH:17]=3)=[O:15])[C:9](=[O:27])[CH2:8]2)=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH2:32](O)[CH3:33]>>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([C:16]3[CH:26]=[CH:25][C:19]([O:20][CH2:21][C:22]([O:24][CH2:32][CH3:33])=[O:23])=[CH:18][CH:17]=3)=[O:15])[C:9](=[O:27])[CH2:8]2)=[CH:3][CH:2]=1

Participants

4

Reactant 3

HCID 702EthanolHCID 24386Thionyl ChlorideHCID 18918395HCID 18918395, compound

Product 1

HCID 18918624Ethyl 4-[2-[4-(4-pyridyl)piperazin-2-one-1-yl]acetyl]phenoxyacetate

Procedure

A crude sample of the product of Example 36 (3.4 g) was treated with a solution, at 0° C., made by adding thionyl chloride (2.25 g) dropwise to ethanol (45 ml) with stirring at below 0° C. The mixture was stirred at room temperature for 2 hours, heated at gentle reflux for 21/2 hours, and evaporated. The residue was treated with water and adjusted to pH6 with aqueous sodium bicarbonate solution. The gum which precipitated was separated and the aqueous solution was adjusted to pH8 and extracted with dichloromethane, (2×50 ml). The combined extracts were washed with brine, dried and evaporated. The residue was purified by chromatography using a 10 g. Mega Bond Elut silica gel column, eluting with 5% methanol/dichloromethane/0.5% triethylamine to give the title product as a solid (0.2 g); m.p. 163°-165° C.; NMR(CDCl3) δ 8.34(2H,m), 7.97(2H,m), 6.98(2H,m), 6.63(2H,m), 4.89(2H,s), 4.7(2H,s), 4.29(2H,q), 4.1(2H,s), 3.7(2H, m), 3.6(2H,m), 1.31(3H,t); m/e 398(M+H)+ ; calculated for C21H23N3 O5 : C, 63.5; M, 5.83; N, 10.6. Found: C, 61.5; H, 5.9; N, 10.5%.

Workup

  1. stirringThe mixture was stirred at room temperature for 2 hours
  2. temperatureheated
  3. temperatureat gentle reflux for 21/2 hours
  4. customevaporated
  5. additionThe residue was treated with water
  6. customThe gum which precipitated
  7. customwas separated
  8. extractionextracted with dichloromethane, (2×50 ml)
  9. washThe combined extracts were washed with brine
  10. customdried
  11. customevaporated
  12. customThe residue was purified by chromatography
  13. washMega Bond Elut silica gel column, eluting with 5% methanol/dichloromethane/0.5% triethylamine

Sources & evidence

ORD record
ord-b36ff282a19946cb9e1721c4f32fd0ac
Source dataset
uspto-grants-1998_03
Patent number
US05728701

Reaction notes

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