Lithium hydroxide, monohydrate → 3-Hydroxy-6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylic acid

HRID 873530Notes

Reaction equation

HRID 873530 reaction equation
O.[OH-].[Li+].[OH:4][C:5]1[C:6]([C:40]([O:42]C)=[O:41])=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([CH:19]3[C:32]4[C:31](=[O:33])[CH2:30][C:29]([CH3:35])([CH3:34])[CH2:28][C:27]=4[O:26][C:25]4[CH2:24][C:23]([CH3:37])([CH3:36])[CH2:22][C:21](=[O:38])[C:20]3=4)[C:12]=2[CH3:39])=[CH:9][CH:10]=1>C1COCC1.O>[OH:4][C:5]1[C:6]([C:40]([OH:42])=[O:41])=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([CH:19]3[C:20]4[C:21](=[O:38])[CH2:22][C:23]([CH3:36])([CH3:37])[CH2:24][C:25]=4[O:26][C:27]4[CH2:28][C:29]([CH3:35])([CH3:34])[CH2:30][C:31](=[O:33])[C:32]3=4)[C:12]=2[CH3:39])=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 117700763Methyl 3-hydroxy-6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylate

Product 1

HCID 1177005523-Hydroxy-6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylic acidYield 39.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (84.6 mg, 2.02 mmol) was added to a solution of the methyl 3-hydroxy-6-[4-methoxy-2-methyl-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylate produced in Example 11-3 (250 mg, 0.46 mmol) in THF (5 ml) and water (2.5 ml) at room temperature, and the mixture thus obtained was then stirred at the same temperature as above for 21 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then washed with diethyl ether. A 1 N aqueous solution of hydrochloric acid (2.02 ml) was added to the water layer, and the solution thus mixed was then extracted with dichloromethane seven times. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (methanol:dichloromethane=3:97 to 6:94, v/v). The fraction thus obtained was washed with a mixed solution of diethyl ether and hexane, followed by collection by filtration and drying, to obtain the title compound (95.6 mg, yield: 39%).

Workup

  1. customthe mixture thus obtained
  2. washthe mixed solution was then washed with diethyl ether
  3. additionA 1 N aqueous solution of hydrochloric acid (2.02 ml) was added to the water layer
  4. additionthe solution thus mixed
  5. extractionwas then extracted with dichloromethane seven times
  6. customThe organic layer thus obtained
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled away under reduced pressure
  9. customthe residue thus obtained
  10. customwas then purified by silica gel column chromatography (methanol:dichloromethane=3:97 to 6:94, v/v)
  11. customThe fraction thus obtained
  12. washwas washed with a mixed solution of diethyl ether and hexane
  13. filtrationfollowed by collection by filtration
  14. customdrying

Sources & evidence

ORD record
ord-7b024e824fc74943aa77f6cd255cf62f
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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