Reaction #2346

Reaction equation

product

4-[2-[4-(4-pyridyl)piperazin-2-one-1-yl]acetyl]-phenoxy acetic acid

thionyl chloride

ethanol

→

title product

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

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature for 2 hours
2. 2
   Temperatureheated
3. 3
   Temperatureat gentle reflux for 21/2 hours
4. 4
   Otherevaporated
5. 5
   workup.ADDITIONThe residue was treated with water
6. 6
   OtherThe gum which precipitated
7. 7
   Otherwas separated
8. 8
   Extractionextracted with dichloromethane, (2×50 ml)
9. 9
   WashThe combined extracts were washed with brine
10. 10
    Otherdried
11. 11
    Otherevaporated
12. 12
    OtherThe residue was purified by chromatography
13. 13
    WashMega Bond Elut silica gel column, eluting with 5% methanol/dichloromethane/0.5% triethylamine

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%.

Source