3-[1-(tert-butyloxycarbonyl)-L-prolylthio]-2-methylpropanoic acid → (4RS-9aS)-hexahydro-4-methyl-1H,5H-pyrrolo[2,1-c][1,4]thiazepine-1,5-dione

HRID 1701390Notes

Reaction equation

HRID 1701390 reaction equation
C(OC([N:8]1[CH2:21][CH2:20][CH2:19][C@H:9]1[C:10]([S:12][CH2:13][CH:14]([CH3:18])[C:15](O)=[O:16])=[O:11])=O)(C)(C)C>FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>[CH3:18][CH:14]1[CH2:13][S:12][C:10](=[O:11])[C@@H:9]2[CH2:19][CH2:20][CH2:21][N:8]2[C:15]1=[O:16]

Participants

4

Reactant 1

HCID 545521053-[1-(tert-butyloxycarbonyl)-L-prolylthio]-2-methylpropanoic acid

Product 1

HCID 22810363(4RS-9aS)-hexahydro-4-methyl-1H,5H-pyrrolo[2,1-c][1,4]thiazepine-1,5-dione

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 7519AnisoleSolvent

Procedure

3-[1-(tert-butyloxycarbonyl)-L-prolylthio]-2-methylpropanoic acid (2.3 g) is dissolved in a mixture of trifluoroacetic acid (15 ml) and anisole (1.1 g). After fifteen minutes at room temperature the mixture is concentrated to dryness in vacuo and the residue triturated with ether-hexane (1:1). The insoluble material is dried in vacuo, dissolved in dichloromethane (100 ml) and added dropwise to a stirred solution of 1-cyclohexyl-3-(2-morpholino-ethyl) carbodiimide metho-p-toluene sulfonate (20 g) in 900 ml of dichloromethane under argon. The reaction mixture is stored at room temperature for three days and the dichloromethane is then removed in vacuo. The residue is dissolved in ethyl acetate and the solution is washed with 10% potassium biculfate, water, saturated sodium bicarbonate and water. The organic layer is dried and concentrated to give the title compound.

Workup

  1. concentrationAfter fifteen minutes at room temperature the mixture is concentrated to dryness in vacuo
  2. customthe residue triturated with ether-hexane (1:1)
  3. customThe insoluble material is dried in vacuo
  4. dissolutiondissolved in dichloromethane (100 ml)
  5. additionadded dropwise to a stirred solution of 1-cyclohexyl-3-(2-morpholino-ethyl) carbodiimide metho-p-toluene sulfonate (20 g) in 900 ml of dichloromethane under argon
  6. customthe dichloromethane is then removed in vacuo
  7. dissolutionThe residue is dissolved in ethyl acetate
  8. washthe solution is washed with 10% potassium biculfate, water, saturated sodium bicarbonate and water
  9. customThe organic layer is dried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-3e32ade1f42f43dd9ad08a6f4dca1328
Source dataset
uspto-grants-1980_03
Patent number
US04192945

Reaction notes

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