Hydrochloric Acid → 3,5-dimethyl-4-hydroxy-6-(5-(5-pyrimidinylmethoxy)benzofuran-2-yl)-2H-pyran-2-one

HRID 1357213Notes

Reaction equation

HRID 1357213 reaction equation
C(P(CCCC)CCCC)CCC.CN(C(/N=N/C(N(C)C)=O)=O)C.C([O:29][C:30]1[C:35]([CH3:36])=[C:34]([C:37]2[O:38][C:39]3[CH:45]=[CH:44][C:43](O)=[CH:42][C:40]=3[CH:41]=2)[O:33][C:32](=[O:47])[C:31]=1[CH3:48])(=O)C.[OH:49][CH2:50][C:51]1[CH:52]=[N:53][CH:54]=[N:55][CH:56]=1.[OH-].[Li+].Cl>C1COCC1.C(Cl)Cl.CCOC(C)=O>[CH3:48][C:31]1[C:32](=[O:47])[O:33][C:34]([C:37]2[O:38][C:39]3[CH:45]=[CH:44][C:43]([O:49][CH2:50][C:51]4[CH:52]=[N:53][CH:54]=[N:55][CH:56]=4)=[CH:42][C:40]=3[CH:41]=2)=[C:35]([CH3:36])[C:30]=1[OH:29]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 13831TributylphosphineHCID 5353800DiamideHCID 15466386(Pyrimidin-5-yl)methanolHCID 185058904-acetyloxy-3,5-dimethyl-6-(5-hydroxybenzofuran-2-yl)-2H-pyran-2-one

Product 1

HCID 547381073,5-dimethyl-4-hydroxy-6-(5-(5-pyrimidinylmethoxy)benzofuran-2-yl)-2H-pyran-2-one

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of tributylphosphine in 2 N THF (0.94 ml) and a solution of TMAD (323 mg) in CH2Cl2 (3 ml) were added dropwise to a solution of 4-acetyloxy-3,5-dimethyl-6-(5-hydroxybenzofuran-2-yl)-2H-pyran-2-one (118 mg) and 5-hydroxymethylpyrimidine (202 mg) in THF (30 ml) at 0° C., and the mixture was stirred at room temperature overnight. The reaction solution was cooled on ice, a 1 N lithium hydroxide aqueous solution (5 ml) was added and the mixture was stirred at room temperature for one hour, after which the reaction solution was again cooled on ice, a 1 N hydrochloric acid aqueous solution (5 ml) and AcOEt were added, the organic layer and aqueous layer were separated, and the aqueous layer was further extracted with AcOEt. The organic layers were combined and dried with MgSO4, and then filtered and concentrated. The residue was purified by silica gel column chromatography (AcOEt/MeOH=10/1) to obtain 3,5-dimethyl-4-hydroxy-6-(5-(5-pyrimidinylmethoxy)benzofuran-2-yl)-2H-pyran-2-one.

Workup

  1. temperatureThe reaction solution was cooled on ice
  2. stirringthe mixture was stirred at room temperature for one hour
  3. temperatureafter which the reaction solution was again cooled on ice
  4. customthe organic layer and aqueous layer were separated
  5. extractionthe aqueous layer was further extracted with AcOEt
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (AcOEt/MeOH=10/1)

Sources & evidence

ORD record
ord-81a702c01d49401bb595755b1d9d5695
Source dataset
uspto-grants-2003_07
Patent number
US06589984B1

Reaction notes

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