Benzoic acid, 2-mercapto-, methyl ester → (+/-)-3-Butyl-3-ethyl-2,3-dihydro-1,4-benzothiazepin-5(4H)-one

HRID 398819Notes

Reaction equation

HRID 398819 reaction equation
[C:1]([O:10]C)(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[CH2:12]([C:16]1([CH2:19][CH3:20])[CH2:18][NH:17]1)[CH2:13][CH2:14][CH3:15]>CO>[CH2:12]([C:16]1([CH2:19][CH3:20])[NH:17][C:1](=[O:10])[C:2]2[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=2[S:4][CH2:18]1)[CH2:13][CH2:14][CH3:15]

Participants

4

Reactant 2

HCID 21009Benzoic acid, 2-mercapto-, methyl esterHCID 217099702-Butyl-2-ethylaziridine

Product 1

HCID 18968861(+/-)-3-Butyl-3-ethyl-2,3-dihydro-1,4-benzothiazepin-5(4H)-oneYield 97.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl thiosalicylate (25.0 g, Aldrich) in methanol (95 ml) at 0° C. was added 2-butyl-2-ethylaziridine (20.0 g, Synthetic Example 1(f)) and the mixture was stirred at room temperature for 18 hours. Solvent was evaporated and toluene (200 ml) and sodium methoxide (8.2 g) were added. The mixture was heated to reflux for 4.5 hours, removing water through a Dean-Stark trap. Solvent was evaporated and the residue was partitioned between 5% HCl (500 ml) and dichloromethane (400 ml). The organic layer was separated, dried and concentrated. Crystallization from hexanes/ethyl acetate provided the title compound as a white solid (38.0 g), mp 92°-93° C. 1H NMR consistent with the proposed structure.

Workup

  1. customSolvent was evaporated
  2. additiontoluene (200 ml) and sodium methoxide (8.2 g) were added
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 4.5 hours
  5. customremoving water through a Dean-Stark trap
  6. customSolvent was evaporated
  7. customthe residue was partitioned between 5% HCl (500 ml) and dichloromethane (400 ml)
  8. customThe organic layer was separated
  9. customdried
  10. concentrationconcentrated
  11. customCrystallization from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-82ff9468691442bb9de9ea51b9fb9413
Source dataset
uspto-grants-1998_10
Patent number
US05817652

Reaction notes

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