Water → HCID 68671102, compound

HRID 2192895Notes

Reaction equation

HRID 2192895 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:12](=[CH:18][CH:19]2[CH2:23][CH2:22][C:21]3([O:28][CH2:27][C:26]([CH3:30])([CH3:29])[CH2:25][O:24]3)[CH2:20]2)[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=[CH:6][C:7]=1[S:8][CH:9]1[CH2:11][CH2:10]1.C1(B(O)[OH:35])CC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH2:45]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:12](=[CH:18][CH:19]2[CH2:23][CH2:22][C:21]3([O:24][CH2:25][C:26]([CH3:29])([CH3:30])[CH2:27][O:28]3)[CH2:20]2)[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH:9]1[CH2:11][CH2:10]1)(=[O:35])=[O:45]

Participants

8

Reactant 4

HCID 962Water2×HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 68671175HCID 68671175, compound

Product 1

HCID 68671102HCID 68671102, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 2-[3-bromo-4-(cyclopropylsulfanyl)phenyl]-3-(8,8-dimethyl-6,10-dioxaspiro[4.5]dec-2-yl)acrylate (2.40 g, (E)/(Z)-mixture), cyclopropylboronic acid (606 mg, 7.05 mmol), and tetrakis(triphenylphosphine)palladium (272 mg, 0.24 mmol) were dissolved in toluene (72 mL), and to this solution were added tripotassium phosphate (1.80 g, 8.46 mmol) and water (3.6 mL). The mixture was stirred at 100° C. for 20 hours. It was cooled to room temperature, and water and ethyl acetate were added thereto. The organic layer was separated, washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography. The obtained intermediate was dissolved in dichloromethane (48 mL), followed by ice-cooling. To this solution were added sodium hydrogen carbonate (3.95 g) and then m-chloroperbenzoic acid (1.30 g). It was warmed to room temperature and stirred for 1 hour. Water was added to the reaction mixture to stop the reaction, and 1 M aqueous sodium sulfite solution was further added thereto. The organic layer was separated and the aqueous layer was then extracted with dichloromethane. The organic layer was further washed with a saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain ethyl 2-[3-bromo-4-(cyclopropylsulfonyl)phenyl]-3-(8,8-dimethyl-6,10-dioxaspiro[4.5]dec-2-yl)acrylate (1.82 g) as an (E)/(Z)-mixture of olefin. The obtained mixture was dissolved in methanol (22.1 mL), and to this solution was slowly added 8 M aqueous potassium hydroxide solution (11.8 mL), which had been separately prepared. After stirring at room temperature for 3 hours, concentrated hydrochloric acid was carefully added to adjust the pH to 1-2. Methanol was evaporated under reduced pressure, followed by carrying out an operation of extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the obtained solid was dried under reduced pressure to obtain (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-(3-oxocyclopentyl)acrylic acid (1.41 g).

Workup

  1. temperatureIt was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography
  7. dissolutionThe obtained intermediate was dissolved in dichloromethane (48 mL)
  8. temperaturecooling
  9. additionTo this solution were added sodium hydrogen carbonate (3.95 g)
  10. temperatureIt was warmed to room temperature
  11. stirringstirred for 1 hour
  12. additionWater was added to the reaction mixture
  13. customthe reaction, and 1 M aqueous sodium sulfite solution
  14. additionwas further added
  15. customThe organic layer was separated
  16. extractionthe aqueous layer was then extracted with dichloromethane
  17. washThe organic layer was further washed with a saturated aqueous sodium hydrogen carbonate solution
  18. dry with materialdried over anhydrous sodium sulfate
  19. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f7b9f287afe848ca9fd34113bc274a8e
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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