Potassium Carbonate → 2-(4-(((Benzyloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid

HRID 1166437Notes

Reaction equation

HRID 1166437 reaction equation
Br[CH2:2][C:3]([O:5]C)=[O:4].[CH2:7]([O:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][NH:21][C:20](=[O:24])[N:19]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:7]([O:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]([CH2:2][C:3]([OH:5])=[O:4])[C:20](=[O:24])[N:19]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 178522340HCID 178522340, compound

Product 1

HCID 7254702-(4-(((Benzyloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

In a three-necked round bottom flask equipped with mechanical stirring and nitrogen inlet was placed methyl bromacetate (7.82 mL, 82.6 mmol) and a suspension of N4-benzyloxycarbonyl-cytosine (9, 21 g, 82.6 mmol) and potassium carbonate (11.4 g, 82.6 mmol) in dry DMF (900 mL). The mixture was stirred vigorously overnight, filtered, and evaporated to dryness, in vacuo. Water (300 mL) and 4 N hydrochloric acid (10 mL) were added, the mixture was stirred for 15 minutes at 0° C., filtered, and washed with water (2×75 mL). The isolated precipitate was treated with water (120 mL), 2N sodium hydroxide (60 mL), stirred for 30 minutes, filtered, cooled to 0° C., and 4 N hydrochloric acid (35 mL) was added. The title compound was isolated by filtration, washed thoroughly with water, recrystallized from methanol (1000 mL) and washed thoroughly with ether. This afforded 7.70 g (31%) of pure title compound. The mother liquor from recrystallization was reduced to a volume of 200 mL and cooled to 0° C. This afforded an additional 2.30 g of a material that was pure by tlc but had a reddish color. M.p. 266-274° C. Anal. for C14H13N3O5. Found(calc.); C, 55.41(55.45); H, 4.23(4.32); N, 14.04(13.86). 1H-NMR (90 MHz; DMSO-d6): 8.02 ppm (d,J=7.32 Hz, 1H, H-6); 7.39 (s, 5H, Ph); 7.01 (d, J=7.32 Hz, 1H, H-5); 5.19 (s, 2H, PhCH2—); 4.52 (s, 2H).

Workup

  1. customIn a three-necked round bottom flask equipped
  2. customnitrogen inlet was placed
  3. stirringThe mixture was stirred vigorously overnight
  4. filtrationfiltered
  5. customevaporated to dryness, in vacuo
  6. additionWater (300 mL) and 4 N hydrochloric acid (10 mL) were added
  7. stirringthe mixture was stirred for 15 minutes at 0° C.
  8. filtrationfiltered
  9. washwashed with water (2×75 mL)
  10. additionThe isolated precipitate was treated with water (120 mL), 2N sodium hydroxide (60 mL)
  11. stirringstirred for 30 minutes
  12. filtrationfiltered
  13. addition4 N hydrochloric acid (35 mL) was added

Sources & evidence

ORD record
ord-e621e238563243f0939b616804aa7cb4
Source dataset
uspto-grants-2003_09
Patent number
US06613873B1

Reaction notes

Loading…