Citric Acid → 4-[5-(2-Fluorophenoxy)oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenol

HRID 1027718Notes

Reaction equation

HRID 1027718 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10].Cl[C:12]1[N:13]=[CH:14][C:15]2[N:20]=[C:19]([C:21]3[CH:26]=[C:25]([CH3:27])[C:24]([OH:28])=[C:23]([CH3:29])[CH:22]=3)[O:18][C:16]=2[N:17]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C(=O)C>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:12]1[N:13]=[CH:14][C:15]2[N:20]=[C:19]([C:21]3[CH:22]=[C:23]([CH3:29])[C:24]([OH:28])=[C:25]([CH3:27])[CH:26]=3)[O:18][C:16]=2[N:17]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 97072-Fluorophenol2×HCID 24758Sodium hydride2×HCID 1363977474-(5-Chlorooxazolo[5,4-d]pyrimidin-2-yl)-2,6-dimethylphenol

Product 1

HCID 1361211154-[5-(2-Fluorophenoxy)oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenol

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
80 °C

Procedure

Under argon, 0.48 g of sodium hydride (60% in mineral oil) is added a little at a time to a solution of 1.12 ml of 2-fluorophenol in 40 ml of dry N,N-dimethylacetamide. After 30 min at room temperature, a suspension of 2.78 g of 4-(5-chlorooxazolo[5,4-d]pyrimidin-2-yl)-2,6-dimethylphenol (see Ex. 1 (c)) in 60 ml of dry N,N-dimethylacetamide is added, and the reaction is stirred at 60° C. for 1.5 h and at 80° C. for 5.5 h. Another 1.12 ml of 2-fluorophenol in 40 ml of dry N,N-dimethylacetamide were then reacted under argon with 0.48 g of sodium hydride (60% in mineral oil), and this mixture was added to the reaction at room temperature. After a further 9 h at 80° C., the reaction was cooled to room temperature and neutralized with 10% strength aqueous citric acid solution. The precipitated solid was filtered off with suction, washed with water and dried under reduced pressure at 45° C. This gave 3.37 g (96%) of the title compound, which was reacted without any further purification.

Workup

  1. additionis added
  2. additionthis mixture was added to the reaction at room temperature
  3. waitAfter a further 9 h at 80° C.
  4. filtrationThe precipitated solid was filtered off with suction
  5. washwashed with water
  6. customdried under reduced pressure at 45° C
  7. customThis gave 3.37 g (96%) of the title compound, which was reacted without any further purification

Sources & evidence

ORD record
ord-dfddc6bccfef455abb853c0b0578450d
Source dataset
uspto-grants-2014_05
Patent number
US08735402B2

Reaction notes

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