Water → 2-(3-Hydroxy-2-naphthoyl)-3-hydroxypyridine

HRID 862066

Reaction equation

HRID 862066 reaction equation
Br[C:2]1[C:7]([O:8]COCC[Si](C)(C)C)=[CH:6][CH:5]=[CH:4][N:3]=1.CCCCC.C([Li])(C)(C)C.COC[O:30][C:31]1[C:32]([C:41](OC)=[O:42])=[CH:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[CH:36][CH:35]=2.O>C1COCC1>[OH:30][C:31]1[C:32]([C:41]([C:2]2[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=2)=[O:42])=[CH:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[CH:36][CH:35]=2

Participants

6

Reactant 4

HCID 962WaterHCID 156089422-Bromo-3-{[2-(trimethylsilyl)ethoxy]methoxy}pyridineHCID 53900226Methyl 3-methoxymethoxy-2-naphthoateHCID 178446069HCID 178446069, compound

Product 1

HCID 197015612-(3-Hydroxy-2-naphthoyl)-3-hydroxypyridineYield 54.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromo-3-(β-trimethylsilylethoxymethoxy)pyridine (8.51 g) in THF (150 ml) was added dropwise at -78° C. a 1.7M t-butyl lithium pentane solution (35 ml) under argon atmosphere, then the mixture was stirred for 20 minutes. To the mixture was then added dropwise at -78° C. a solution of methyl 3-methoxymethoxy-2-naphthoate (6.68 g) in THF (50 ml). The mixture was warmed up to room temperature and stirred for 2 hours, to which was added water to quench the reaction, followed by extraction with ethyl acetate. The organic layer was dried (anhydrous magnesium sulfate), then the solvent was distilled off under reduced pressure. To the residue were added acetone (200 ml) and 1N sulfuric acid (36 ml), then the mixture was stirred for 5 hours at 50°-60° C. The reaction mixture was cooled by aeration, which was then neutralized with a saturated aqueous solution of sodium hydrogencarbonate, followed by extraction with chloroform. The organic layer was dried (anhydrous magnesium sulfate), then the solvent was distilled off under reduced pressure. The residue was purified by means of a silica gel column chromatography (eluted with ethyl acetate/hexane) to give 2-(3-hydroxy-2-naphthoyl)-3-hydroxypyridine (3.93 g) (Compound A-21). The physical properties and spectrum data are shown in Table 1 and Table 5.

Workup

  1. stirringstirred for 2 hours, to which
  2. customto quench
  3. customthe reaction
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe organic layer was dried (anhydrous magnesium sulfate)
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionTo the residue were added acetone (200 ml) and 1N sulfuric acid (36 ml)
  8. stirringthe mixture was stirred for 5 hours at 50°-60° C
  9. temperatureThe reaction mixture was cooled by aeration, which
  10. extractionfollowed by extraction with chloroform
  11. dry with materialThe organic layer was dried (anhydrous magnesium sulfate)
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe residue was purified by means of a silica gel column chromatography (eluted with ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3599534fe633406da102a0124447e59b
Source dataset
uspto-grants-1998_02
Patent number
US05716971

Linked notes

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