Citric Acid → (3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propoxy)acetic acid

HRID 1926939Notes

Reaction equation

HRID 1926939 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:16]([O:18][CH2:19][CH2:20][CH2:21][OH:22])=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:5][CH:4]=1.C([O:33][C:34](=[O:37])[CH2:35]Br)(C)(C)C.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:17]3[C:16]([O:18][CH2:19][CH2:20][CH2:21][O:22][CH2:35][C:34]([OH:37])=[O:33])=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 580167773-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propan-1-ol

Product 1

HCID 25096163(3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propoxy)acetic acid

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Put 200 mg (0.53 mmol) 3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propan-1-ol with 518 mg (2.66 mmol) bromoacetic acid tert.-butyl ester and 36 mg (0.106 mmol) tetra-n-butylammonium hydrogensulphate in 5 ml dichloromethane and cool to 0° C. Add 1.0 ml 50% sodium hydroxide solution and stir vigorously at 0° C. Then leave to return to RT and continue stirring vigorously overnight. Then dilute with dichloromethane and water, acidify with 10% citric acid solution and separate the phases. Re-extract the aqueous phase once with dichloromethane. Combine the organic phases, wash once with satd. sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. Dissolve the residue in 5 ml dichloromethane. Add 1.25 ml TFA and stir for 2 h at RT. Then concentrate by evaporation and dry at high vacuum. Purify the residue chromatographically on a silica-gel thick-layer plate (solvent: dichloromethane/methanol 95:5). Extract the product zone with dichloromethane/methanol 9:1. 50 mg (23.0% of theor.) of the target compound is obtained.

Workup

  1. customThen leave
  2. customto return to RT
  3. stirringcontinue stirring vigorously overnight
  4. customseparate the phases
  5. washwash once with satd
  6. dry with materialsodium chloride solution, dry over magnesium sulphate
  7. concentrationconcentrate by evaporation
  8. dissolutionDissolve the residue in 5 ml dichloromethane
  9. additionAdd 1.25 ml TFA
  10. stirringstir for 2 h at RT
  11. concentrationThen concentrate by evaporation
  12. customdry at high vacuum
  13. customPurify the residue chromatographically on a silica-gel thick-layer plate (solvent: dichloromethane/methanol 95:5)
  14. extractionExtract the product zone with dichloromethane/methanol 9:1
  15. custom50 mg (23.0% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-c91b58b62b7146ab867ef869918bffaf
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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