Potassium Carbonate → tert-Butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]piperidine-1-carboxylate

HRID 906456Notes

Reaction equation

HRID 906456 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[C:5]2[SH:13].CS(O[CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[C:5]2[S:13][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidineHCID 57439914HCID 57439914, compound

Product 1

HCID 67130258tert-Butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]piperidine-1-carboxylateYield 33.2%

Procedure

To 6-bromo-4-sulfanylisoquinolin-1(2H)-one (Example 58a, 0.62 g) was added tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (0.676 g) and potassium carbonate (0.769 g). After thoroughly flushing with nitrogen, DMF (6 mL) was added and the reaction stirred at room temperature for 30 min. Further DMF (9 mL) was added, and the reaction stirred at 40° C. for 1 h. Further DMF (10 mL) was added and the reaction stirred at 50° C. for 16 h. The reaction was partitioned between ethyl acetate and water. The aqueous was extracted with further ethyl acetate (3×) and the combined organics were washed with saturated brine (3×100 mL). The organics were dried (MgSO4), filtered and evaporated under reduced pressure. DCM was added, and the resulting suspension was filtered. The filtrate was concentrated under reduced pressure, dissolved in the minimum volume of DCM and purified (SiO2 chromatography, elution with 50%-100% diethyl ether/isohexane followed by ethyl acetate flush) to afford the subtitle compound (0.353 g).

Workup

  1. customAfter thoroughly flushing with nitrogen, DMF (6 mL)
  2. additionwas added
  3. additionFurther DMF (9 mL) was added
  4. stirringthe reaction stirred at 40° C. for 1 h
  5. additionFurther DMF (10 mL) was added
  6. stirringthe reaction stirred at 50° C. for 16 h
  7. customThe reaction was partitioned between ethyl acetate and water
  8. extractionThe aqueous was extracted with further ethyl acetate (3×)
  9. washthe combined organics were washed with saturated brine (3×100 mL)
  10. dry with materialThe organics were dried (MgSO4)
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. additionDCM was added
  14. filtrationthe resulting suspension was filtered
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. dissolutiondissolved in the minimum volume of DCM
  17. custompurified
  18. wash(SiO2 chromatography, elution with 50%-100% diethyl ether/isohexane followed by ethyl acetate flush)

Sources & evidence

ORD record
ord-4cd985742d4e43399eefb7386972d6ba
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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