Citric Acid → (+/-)-6-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}heptanoic acid methyl ester

HRID 1926931Notes

Reaction equation

HRID 1926931 reaction equation
[CH3:1][O:2][C:3](=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7][CH:8]([OH:10])[CH3:9].Cl[C:13]1[C:14]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)=[C:20]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[O:19][C:15]=2[N:16]=[CH:17][N:18]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[CH3:1][O:2][C:3](=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7][CH:8]([O:10][C:13]1[C:14]2[C:21]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)=[C:20]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[O:19][C:15]=2[N:16]=[CH:17][N:18]=1)[CH3:9]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 13085553Methyl 6-hydroxyheptanoateHCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 58016834(+/-)-6-{[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}heptanoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Put 1.902 g (11.9 mmol) (+/−)-6-hydroxyheptanoic acid methyl ester under argon in 20 ml THF and cool to 0° C. Add 6 ml (11.9 mmol) of a 2 M solution of the phosphazene base P2-tert.-butyl in THF and stir for a further 10 min at RT. Then cool to 0° C. again. Add 2.00 g (5.94 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and then stir for a further 1 h at RT. Dilute with water, acidify with 10% aqueous citric acid solution and extract twice with ethyl acetate. Combine the ethyl acetate phases and wash once with satd. sodium chloride solution. Dry over magnesium sulphate, concentrate by evaporation and purify the residue by column chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1). 1.38 g (78.0% of theor.) of the target compound is obtained.

Workup

  1. temperatureThen cool to 0° C. again
  2. stirringstir for a further 1 h at RT
  3. extractionextract twice with ethyl acetate
  4. washwash once with satd
  5. dry with materialDry over magnesium sulphate
  6. concentrationconcentrate by evaporation
  7. custompurify the residue by column chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1)
  8. custom1.38 g (78.0% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-e574523c37d148c0994f5e68df342255
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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