Citric Acid → 3-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propan-1-ol

HRID 1926898Notes

Reaction equation

HRID 1926898 reaction equation
[CH2:1]([OH:5])[CH2:2][CH2:3][OH:4].Cl[C:7]1[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)=[C:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:13][C:9]=2[N:10]=[CH:11][N:12]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.ClCCl.O>[CH3:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([C:15]2[C:8]3[C:7]([O:4][CH2:3][CH2:2][CH2:1][OH:5])=[N:12][CH:11]=[N:10][C:9]=3[O:13][C:14]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 311Citric AcidHCID 104421,3-PropanediolHCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 580167773-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propan-1-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Put 1.13 g (14.85 mmol) 1,3-propanediol in 30 ml THF. Add 833 mg (7.42 mmol) potassium tert.-butylate and stir for 15 min at RT. Then cool to 0° C. and add a solution of 1.0 g (2.97 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine in 15 ml THF dropwise over a time of 30 min. Then leave to return to RT and stir for a further 2 h. Dilute with dichloromethane and water, acidify with 10% citric acid solution and separate the phases. Extract the aqueous phase once with dichloromethane. Combine the organic phases and wash once with satd. sodium chloride solution. Dry over magnesium sulphate, concentrate by evaporation and purify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 7:3→1:1). 772 mg (69.0% of theor.) of the target compound is obtained.

Workup

  1. temperatureThen cool to 0° C.
  2. customThen leave
  3. customto return to RT
  4. stirringstir for a further 2 h
  5. customseparate the phases
  6. extractionExtract the aqueous phase once with dichloromethane
  7. washwash once with satd
  8. dry with materialDry over magnesium sulphate
  9. concentrationconcentrate by evaporation
  10. custompurify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 7:3→1:1)
  11. custom772 mg (69.0% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-6b7d327ef5ca4a26aa339abf1fe578b7
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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