Triphenylphosphine → HCID 59570927, compound

HRID 2192900Notes

Reaction equation

HRID 2192900 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50]4([O:54][C@H:53]([C:55]5[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=5)[C@@H:52]([C:61]5[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=5)[O:51]4)[CH2:49]3)/[C:44](O)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:30][CH2:29]1.[NH2:69][C:70]1[CH:79]=[CH:78][C:73]([C:74]([O:76]C)=[O:75])=[CH:72][N:71]=1>ClCCl.N1C=CC=CC=1.O>[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50]4([O:54][C@H:53]([C:55]5[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=5)[C@@H:52]([C:61]5[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=5)[O:51]4)[CH2:49]3)/[C:44]([NH:69][C:70]3[CH:79]=[CH:78][C:73]([C:74]([OH:76])=[O:75])=[CH:72][N:71]=3)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:41][CH2:42]2)(=[O:39])=[O:38])[CH2:29][CH2:30]1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 737487Methyl 6-aminonicotinateHCID 59571019HCID 59571019, compound

Product 1

HCID 59570927HCID 59570927, compoundYield 26.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphenylphosphine (607 mg) in dichloromethane (10 mL) was added N-bromosuccinimide (412 mg) under ice-cooling, followed by stirring for 15 minutes under ice-cooling. A solution of (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]acrylic acid (600 mg) in dichloromethane (10 mL) was added thereto under ice-cooling, followed by stirring at room temperature for 0.5 hour. A solution of methyl 6-aminonicotinate (160 mg) in dichloromethane (10 mL) and pyridine (0.17 mL) were added thereto at room temperature, followed by stirring at room temperature overnight. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and dried over anhydrous magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1). To the solution of the obtained pale yellow amorphous dioxane (4 mL) was added a 1 M aqueous sodium hydroxide solution (1.2 mL), followed by stirring at 50° C. for 1 hour. 1 M Hydrochloric acid was added thereto to adjust the pH to 2, and then saturated brine was added thereto. The mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate. The crude product obtained by concentration was purified by silica gel column chromatography (hexane:ethyl acetate=1:1-3:1) to obtain 6-({(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]prop-2-enoyl}amino)nicotinic acid (194 mg) as a white amorphous substance.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. temperatureunder ice-cooling
  4. stirringby stirring at room temperature for 0.5 hour
  5. customat room temperature
  6. stirringby stirring at room temperature overnight
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe organic layer was sequentially washed with 1 M hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe crude product obtained by concentration
  11. customwas purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1)
  12. additionTo the solution of the obtained pale yellow amorphous dioxane (4 mL) was added a 1 M aqueous sodium hydroxide solution (1.2 mL)
  13. stirringby stirring at 50° C. for 1 hour
  14. addition1 M Hydrochloric acid was added
  15. additionsaturated brine was added
  16. extractionThe mixture was extracted with chloroform
  17. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  18. customThe crude product obtained by concentration
  19. customwas purified by silica gel column chromatography (hexane:ethyl acetate=1:1-3:1)

Sources & evidence

ORD record
ord-ab46c30df77949ec93afa852fac158f8
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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