Acetic Acid → HCID 18442427, compound

HRID 458940Notes

Reaction equation

HRID 458940 reaction equation
[O:1]=[S:2]1(=[O:30])[C:8]2[CH:9]=[C:10]([O:13]C)[CH:11]=[CH:12][C:7]=2[N:6]([C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:5][C:4]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3]1.C[S-].[Na+].C(O)(=O)C.O>CN(C=O)C>[O:30]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([OH:13])[CH:11]=[CH:12][C:7]=2[N:6]([C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:5][C:4]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 4378561Sodium methanethiolateHCID 18442428HCID 18442428, compound

Product 1

HCID 18442427HCID 18442427, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,1-Dioxo-3,3-dibutyl-5-(4-aminophenyl)-8-methoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 105; 918 mg, 2.13 mmol) was dissolved in DMF (dry, 20 ml). Sodium thiomethoxide (810 mg, 11.6 mmol) was added. The reaction mixture was treated at 100–120° C. for four hours then room temperature overnight. Acetic acid (3 ml) was added and the mixture was flushed with nitrogen (g) and the gas was lead through a flask containing sodium hypochlorite in order to destroy the methyl mercaptan formed. Water was added and the water layer was extracted two times with EtOAc. The combined organic layer was washed with brine, dried, filtered and evaporated under reduced pressure. The mixture contained DMF so toluene and brine was added (everything didn't dissolved). The water layer was extracted two times with toluene. The combined organic layers were washed once with brine. The separation funnel was washed with EtOAc in order to dissolve everything. The toluene and EtOAc solutions were combined, dried, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography using DCM:EtOAc, 7:3 as eluent to give the title compound 0.6 g (27%). M/z 417.4.

Workup

  1. additionThe reaction mixture was treated at 100–120° C. for four hours
  2. customroom temperature overnight
  3. customthe mixture was flushed with nitrogen (g)
  4. additioncontaining sodium hypochlorite in order
  5. customto destroy the methyl mercaptan
  6. customformed
  7. extractionthe water layer was extracted two times with EtOAc
  8. washThe combined organic layer was washed with brine
  9. customdried
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. additionwas added
  13. dissolution(everything didn't dissolved)
  14. extractionThe water layer was extracted two times with toluene
  15. washThe combined organic layers were washed once with brine
  16. washThe separation funnel was washed with EtOAc in order
  17. dissolutionto dissolve everything
  18. customdried
  19. filtrationfiltered
  20. customevaporated under reduced pressure
  21. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-71c72aeab44a4853a13892ac8b52120c
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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