Water → 7-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 50959Notes

Reaction equation

HRID 50959 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][CH2:9][CH2:8][C:7](=[O:11])[C:6]=2[CH:12]=1.Cl.[NH2:14]O.C([O-])(=O)C.[Na+].O>C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][CH2:9][CH2:8][C:7](=[O:11])[NH:14][C:6]=2[CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 813802,3-dihydro-6-methyl-4H-1-benzothiopyran-4-oneHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium Acetate

Product 1

HCID 45944607-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-Methyl-2,3-dihydro-4H-1-benzothiopyran-4-one (2g, 10.9 mmol) was dissloved in 80% ethanol (73 mL) and to this was added hydroxylamine hydrochloride (840 mg, 12.05 mmol) and sodium acetate (990 mg, 12.03 mmol). This mixture was heated at reflux for 3 hours. Water (150 mL) was added and then extracted with dichloromethane (3×100 mL), washed with brine (75 mL), water (75 mL), dried (sodium sulfate) and concentrated to residue. The residue was taken up in polyphosphoric acid (10 mL) and heated at reflux for 1 hour. Ice chips were added and water was added (100 mL) this was stirred for 1 hour. A solid formed and was filtered and purified by flashcolumn chromatography on 20 g of silica gel, eluting with (50%, 60%, and 70%) ethyl acetate in hexanes to give 7-methyl-2,3,4,5-tetrahydrobenzo[b]1,4-thiazepin-4-one (500 mg, 30%). 1H NMR (CDCl3, 300 MHz): δ7.87 (s-broad, 1H), 7.47 (d, 1H, J=7.7 Hz), 6.98 (d, 1H, J=8.1 Hz), 6.91 (s, 1H), 3.42 (t, 2H, J=6.9 Hz), 2.62 (t, 2H, J=6.9 Hz), 2.35 (s, 3H) ppm.

Workup

  1. temperatureThis mixture was heated
  2. temperatureat reflux for 3 hours
  3. extractionextracted with dichloromethane (3×100 mL)
  4. washwashed with brine (75 mL), water (75 mL)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated to residue
  7. temperatureheated
  8. temperatureat reflux for 1 hour
  9. additionIce chips were added
  10. additionwater was added (100 mL)
  11. customA solid formed
  12. filtrationwas filtered
  13. custompurified by flashcolumn chromatography on 20 g of silica gel
  14. washeluting with (50%, 60%, and 70%) ethyl acetate in hexanes

Sources & evidence

ORD record
ord-90bbc8082fd541be89254d5e23b09e52
Source dataset
uspto-grants-2004_03
Patent number
US06713471B1

Reaction notes

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