Triethylamine → Methyl 2-(cyclobutylsulfanyl)benzoate

HRID 1667582Notes

Reaction equation

HRID 1667582 reaction equation
[CH3:1][S:2][C:3]1[C:4](=[CH:8][CH:9]=[CH:10][CH:11]=1)[C:5]([O-:7])=[O:6].[CH2:12](N(CC)CC)C.[CH:19]1(Br)[CH2:22]C[CH2:20]1.C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[Na+]>CN(C=O)C.C(Cl)Cl>[CH:1]1([S:2][C:3]2[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=2[C:5]([O:7][CH3:12])=[O:6])[CH2:22][CH2:19][CH2:20]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 78110BromocyclobutaneHCID 6932478Methylthiosalicylate

Product 1

HCID 57448173Methyl 2-(cyclobutylsulfanyl)benzoateYield 113.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To methylthiosalicylate (3.92 mL, 28.5 mmol) in DMF at 0° C. was added triethylamine (3.97 mL, 28.5 mmol) then cyclobutyl bromide (5.00 g, 37.0 mmol). The ice bath was removed and the reaction was stirred at rt for 1 h then heated to 50° C. overnight. After cooling to rt, diethyl ether was added and the mixture was filtered. The filtrate was diluted with ethyl acetate, then washed with water (6×) and brine (1×). The organic layer was dried (MgSO4), filtered and concentrated to provide a yellow oil. The yellow oil was dissolved in CH2Cl2 (143 mL) and MCPBA (˜75%, 19.7 g, ca. 85.5 mmol) was added. The reaction was stirred for 2.5 h, then was cooled to 0° C. 1 N NaOH was added, and the reaction was stirred for 5 min. The layers were separated, and the organic layer was washed with 1 N NaOH (2×). The aqueous layer was back-extracted with CH2Cl2. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated to provide 2A as a clear oil (7.20 g). LC-MS: 255.01 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. temperaturethen heated to 50° C. overnight
  3. temperatureAfter cooling to rt
  4. additiondiethyl ether was added
  5. filtrationthe mixture was filtered
  6. additionThe filtrate was diluted with ethyl acetate
  7. washwashed with water (6×) and brine (1×)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide a yellow oil
  12. stirringThe reaction was stirred for 2.5 h
  13. temperaturewas cooled to 0° C
  14. stirringthe reaction was stirred for 5 min
  15. customThe layers were separated
  16. washthe organic layer was washed with 1 N NaOH (2×)
  17. extractionThe aqueous layer was back-extracted with CH2Cl2
  18. washThe combined organic layers were washed with brine
  19. dry with materialdried (MgSO4)
  20. filtrationfiltered
  21. concentrationconcentrated

Sources & evidence

ORD record
ord-912ae614ecf74899a66370d57a519b3f
Source dataset
uspto-grants-2011_10
Patent number
US08044242B2

Reaction notes

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