Citric Acid → HCID 25096161, compound

HRID 1926937Notes

Reaction equation

HRID 1926937 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][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22])=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:5][CH:4]=1.[C:31]([O:35][C:36](=[O:39])[CH2:37]Br)([CH3:34])([CH3:33])[CH3:32].[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>[C:31]([O:35][C:36](=[O:39])[CH2:37][O:22][CH2:21][C:20]([CH3:24])([CH3:23])[CH2:19][O:18][C:16]1[C:17]2[C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[C:10]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[O:11][C:12]=2[N:13]=[CH:14][N:15]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 58016880HCID 58016880, compound

Product 1

HCID 25096161HCID 25096161, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Put 300 mg (0.742 mmol) 3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-2,2-dimethylpropan-1-ol with 723 mg (3.71 mmol) bromoacetic acid tert.-butyl ester and 50 mg (0.148 mmol) tetra-n-butylammonium hydrogensulphate in 6 ml dichloromethane. Cool to 0° C. Then add 750 μl 50% sodium hydroxide solution and stir vigorously for a few minutes at 0° C. Stirring vigorously, allow to return to RT, and continue stirring vigorously overnight. Then dilute with dichloromethane and lightly acidify with 10% citric acid solution. Separate the phases and extract the aqueous phase once with dichloromethane. Combine the organic phases and wash once with satd. sodium chloride solution, dry over magnesium sulphate and concentrate by evaporation. Purify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1). 295 mg (76.7% of theor.) of the target compound is obtained.

Workup

  1. stirringStirring vigorously
  2. customto return to RT
  3. stirringcontinue stirring vigorously overnight
  4. customSeparate the phases
  5. extractionextract the aqueous phase once with dichloromethane
  6. washwash once with satd
  7. dry with materialsodium chloride solution, dry over magnesium sulphate
  8. concentrationconcentrate by evaporation
  9. customPurify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1)
  10. custom295 mg (76.7% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-d7b1673832bc45d6aa134543d78fe706
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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