Dimethylformamide → [4-N-(Piperonyloxycarbonyl)-cytosin-1-yl]-acetic acid ethyl ester

HRID 857543Notes

Reaction equation

HRID 857543 reaction equation
[N:1]1([CH2:9][C:10]([OH:12])=[O:11])[CH:8]=[CH:7][C:5]([NH2:6])=[N:4][C:2]1=[O:3].C(N1C=CN=C1)(N1[CH:19]=[CH:18]N=C1)=O.[CH2:25]([OH:35])[C:26]1[CH:34]=[CH:33][C:32]2[O:31][CH2:30][O:29][C:28]=2[CH:27]=1.CN([CH:39]=[O:40])C>>[CH2:18]([O:11][C:10](=[O:12])[CH2:9][N:1]1[CH:8]=[CH:7][C:5]([NH:6][C:39]([O:35][CH2:25][C:26]2[CH:34]=[CH:33][C:32]3[O:31][CH2:30][O:29][C:28]=3[CH:27]=2)=[O:40])=[N:4][C:2]1=[O:3])[CH3:19]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10322Piperonyl alcoholHCID 682631,1'-CarbonyldiimidazoleHCID 21868458HCID 21868458, compound

Product 1

HCID 68524231[4-N-(Piperonyloxycarbonyl)-cytosin-1-yl]-acetic acid ethyl esterYield 96%

Conditions

Temperature
100 °C

Procedure

The reaction mixture of (cytosin-1-yl)-acetic acid (3.94 g, 20 mmol) and 1,1′-carbonyldiimidazole (4.86 g, 30 mmol) in DMF was stirred for 25 min. at 100° C. Then, piperonyl alcohol (6.08 g, 40 mmol) was added to the reaction mixture. The resulting reaction mixture was allowed to cool to room temperature for 2 h. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with water (100 mL×2), dried over MgSO4, and filtered. The filtrate was concentrated in vacuo and treated with ethyl ether to afford white solid. The solid was filtered off and dried in vacuo to give the desired product (7.20 g, 96%). 1H-NMR (500 MHz; DMSO-d6) δ 10.77 (s, 1H), 8.04 (d, 1H), 7.04 (d, 1H), 7.00 (s, 1H), 6.92 (s, 2H), 6.02 (s, 2H), 5.09 (s, 2H), 4.61 (s, 2H), 4.15 (q, 2H), 1.19 (t, 3H).

Workup

  1. customThe resulting reaction mixture
  2. temperatureto cool to room temperature for 2 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (100 mL)
  5. washThe solution was washed with water (100 mL×2)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. additiontreated with ethyl ether
  10. customto afford white solid
  11. filtrationThe solid was filtered off
  12. customdried in vacuo

Sources & evidence

ORD record
ord-23d343ff69ab4a0f89e482a2ebd741f4
Source dataset
uspto-grants-2006_12
Patent number
US07145006B2

Reaction notes

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