Potassium Carbonate → HCID 86672588, compound

HRID 470669Notes

Reaction equation

HRID 470669 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([C@@H:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[C:17]=4[F:23])[C@H:14]([C:24]([OH:26])=[O:25])[N:13]([C@H](C4C=CC=CC=4)[C@@H](O)C4C=CC=CC=4)[C:12]43[CH2:46][CH2:45][C:44]([CH3:48])([CH3:47])[CH2:43][CH2:42]4)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[N+]([O-])([O-])=O.[NH4+].[NH4+].[Ce+4].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.C(=O)([O-])[O-].[K+].[K+]>CO.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([C@@H:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([Cl:22])[C:17]=4[F:23])[C@H:14]([C:24]([OH:26])=[O:25])[NH:13][C:12]43[CH2:46][CH2:45][C:44]([CH3:48])([CH3:47])[CH2:43][CH2:42]4)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 180504Ceric ammonium nitrateHCID 86672586(4'S,5'R)-6''-chloro-4'-(2-chloro-3-fluoropyridin-4-yl)-1'-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-4,4-dimethyl-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxylic acid

Product 1

HCID 86672588HCID 86672588, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The compound (630 mg, 0.94 mmol) obtained in Step 1 of Example 16 was dissolved in acetonitrile (10 ml) and water (4 ml), potassium carbonate (130 mg, 0.94 mmol) was added and the resulting mixture was heated to reflux at 85° C. for 16 hours. After cooling, anhydrous magnesium sulfate (113 mg, 0.94 mmol) was added and the resulting mixture was stirred at room temperature for 15 minutes. After extraction with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give (4′S,5′R)-6″-chloro-4′-(2-chloro-3-fluoropyridin-4-yl)-1′-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-4,4-dimethyl-2″-oxo-1″,2″-dihydrodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indole]-5′-carboxylic acid (650 mg, 100%) as a pale orange amorphous solid [MS (ESI) m/z: 688 (M+H)+.]. The carboxylic acid (650 mg, 0.94 mmol) obtained was dissolved in methanol (30 ml) and water (8 ml), cerium (IV) diammonium nitrate (1.55 g, 2.82 mmol) was added under ice cooling and the resulting mixture was stirred at the same temperature for 30 minutes. Potassium carbonate (780 mg, 5.64 mmol) was added under ice cooling and the resulting mixture was stirred at the same temperature for 1 hour. Insoluble matter was removed by filtration through celite, then the filtrate was concentrated under reduced pressure and water was added to the residue obtained, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was purified by silica gel column chromatography [chloroform:methanol=20:1→4:1 (v/v)] to give 152 mg (33%) of the title compound as a colorless solid.

Workup

  1. stirringthe resulting mixture was stirred at the same temperature for 1 hour
  2. customInsoluble matter was removed by filtration through celite
  3. concentrationthe filtrate was concentrated under reduced pressure and water
  4. additionwas added to the residue
  5. customobtained
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue obtained
  11. customwas purified by silica gel column chromatography [chloroform:methanol=20:1→4:1 (v/v)]

Sources & evidence

ORD record
ord-631de90efc254b818acf6ccd9feb1300
Source dataset
uspto-grants-2014_01
Patent number
US08629133B2

Reaction notes

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