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

HRID 1926914Notes

Reaction equation

HRID 1926914 reaction equation
[CH3:1][O:2][CH:3]([CH2:6][OH:7])[CH2:4][OH:5].Cl[C:9]1[C:10]2[C:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:15][C:11]=2[N:12]=[CH:13][N:14]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OC)(C)(C)C.O>[CH3:1][O:2][CH:3]([CH2:6][O:7][C:9]1[C:10]2[C:17]([C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)=[C:16]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[O:15][C:11]=2[N:12]=[CH:13][N:14]=1)[CH2:4][OH:5]

Participants

7

Reactant 3

HCID 311Citric AcidHCID 111709312-Methoxypropane-1,3-diolHCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 58016954(+/-)-2-Methoxy-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}propan-1-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

Put 1.014 g (9.65 mmol) 2-methoxypropane-1,3-diol in 20 ml THF. Add 542 mg (4.825 mmol) potassium tert.-butylate and stir for 15 min at RT. Then cool to 0° C. and add a solution of 650 mg (1.93 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine in 10 ml THF dropwise in the space of 30 min. Then leave to return to RT and stir overnight at RT. Next, dilute with tert.-butylmethyl ether and water. Acidify with 10% citric acid solution and separate the phases. Re-extract the aqueous phase once with tert.-butylmethyl ether. Combine the organic phases and wash once with satd. sodium chloride solution. Then dry over magnesium sulphate and concentrate by evaporation. Purify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 7:3); 587 mg (74.8% 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 overnight at RT
  5. customseparate the phases
  6. washwash once with satd
  7. dry with materialThen dry over magnesium sulphate
  8. concentrationconcentrate by evaporation
  9. customPurify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 7:3)
  10. custom587 mg (74.8% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-c66f78d5d9bf4b85829f5b6b05c50ba6
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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