Water → 1-{6-[4-Methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridin-2-yl}-D-proline

HRID 873535Notes

Reaction equation

HRID 873535 reaction equation
[OH-].[Li+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[C:15]([N:17]3[CH2:25][CH2:24][CH2:23][C@@H:18]3[C:19]([O:21]C)=[O:20])[CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[CH:26]1[C:39]2[C:38](=[O:40])[CH2:37][C:36]([CH3:42])([CH3:41])[CH2:35][C:34]=2[O:33][C:32]2[CH2:31][C:30]([CH3:44])([CH3:43])[CH2:29][C:28](=[O:45])[C:27]1=2.C1COCC1.O.O>C(OCC)C>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:16]=[C:15]([N:17]3[CH2:25][CH2:24][CH2:23][C@@H:18]3[C:19]([OH:21])=[O:20])[CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[CH:26]1[C:27]2[C:28](=[O:45])[CH2:29][C:30]([CH3:43])([CH3:44])[CH2:31][C:32]=2[O:33][C:34]2[CH2:35][C:36]([CH3:42])([CH3:41])[CH2:37][C:38](=[O:40])[C:39]1=2

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 21881883Oxolane--water (1/1)HCID 117700856HCID 117700856, compound

Product 1

HCID 1177008051-{6-[4-Methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridin-2-yl}-D-prolineYield 70%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Lithium hydroxide (16.9 mg, 403 μmol) was added to a solution of the methyl 1-{6-[4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridin-2-yl}-D-prolinate obtained in Example 15-2 (157 mg, 269 μmol) in a mixed solvent of THF/water (2:1, v/v) (3 mL) at room temperature. The mixture thus obtained was stirred at the same temperature as above for 30 minutes, and was further stirred at 60° C. for 1 hour. Thereafter, water and diethyl ether were added to the reaction solution, and the mixed solution was then extracted with water twice. The resultant was washed with diethyl ether. Thereafter, 1 N hydrochloric acid was added to the water layer thus obtained, so that the pH was adjusted to pH 4 or lower, and the mixed solution was then extracted with ethyl acetate three times. The organic layer thus obtained was dried over anhydrous magnesium sulfate, and the solvent was then distilled away under reduced pressure. The residue obtained was crystallized from hexane/ethyl acetate to obtain the title compound (107 mg, yield: 70%).

Workup

  1. customat room temperature
  2. customThe mixture thus obtained
  3. stirringwas further stirred at 60° C. for 1 hour
  4. extractionthe mixed solution was then extracted with water twice
  5. washThe resultant was washed with diethyl ether
  6. additionThereafter, 1 N hydrochloric acid was added to the water layer
  7. customthus obtained, so that the pH
  8. extractionlower, and the mixed solution was then extracted with ethyl acetate three times
  9. customThe organic layer thus obtained
  10. dry with materialwas dried over anhydrous magnesium sulfate
  11. distillationthe solvent was then distilled away under reduced pressure
  12. customThe residue obtained
  13. customwas crystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-0cf1099f448344a992a296f23255ceaf
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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