Trifluoroacetic acid → HCID 58911555, compound

HRID 1296306Notes

Reaction equation

HRID 1296306 reaction equation
FC(F)(F)C(O)=O.[CH2:8]1[CH:17]2[N:12]([S:13](=[O:23])(=[O:22])[C:14]3[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=3[CH2:16]2)[CH2:11][CH2:10][N:9]1C(OC(C)(C)C)=O>>[CH2:8]1[CH:17]2[N:12]([S:13](=[O:22])(=[O:23])[C:14]3[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=3[CH2:16]2)[CH2:11][CH2:10][NH:9]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68688736HCID 68688736, compound

Product 1

HCID 58911555HCID 58911555, compound

Procedure

Cold trifluoroacetic acid (2 mL) was added to cold 1,1-dimethylethyl 1,2,3,4,11,11a-hexahydropyrazino[1,2-b][1,2]benzothiazine-2-carboxylate 6,6-dioxide (151 mg, 0.446 mmol). After 1 h, the reaction was concentrated in vacuo. The residue was partitioned between dichloromethane (10 mL) and 0.5 N sodium carbonate (2 mL). The organic layer was dried (sodium sulfate) and concentrated in vacuo. The residue was chromatographed (Diacel Chiracel OJ, 5×50 cm, 35% 1:1 methanol/ethanol:hexanes containing 0.3% triethylamine, 50 mL/min). Fractions containing the more rapidly eluting enantiomer concentrated in vacuo. The residue was taken up in 50% aqueous methanol (1 mL) and was loaded onto a 1-g methanol-activated water-equilibrated SCX-type cation exchange column. The column was washed with water (5 mL) and 25% aqueous methanol (5 mL). The column was eluted with 2 N methanolic ammonia. Concentration of this fraction in vacuo provided (−)1,2,3,4,11,11a-hexahydropyrazino[1,2-b][1,2]benzothiazine 6,6-dioxide: LCMS (pos. ion spectrum) m/z 239.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customThe residue was partitioned between dichloromethane (10 mL) and 0.5 N sodium carbonate (2 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed (Diacel Chiracel OJ, 5×50 cm, 35% 1:1 methanol/ethanol:hexanes containing 0.3% triethylamine, 50 mL/min)
  6. additionFractions containing the
  7. washmore rapidly eluting enantiomer
  8. concentrationconcentrated in vacuo
  9. washThe column was washed with water (5 mL) and 25% aqueous methanol (5 mL)
  10. washThe column was eluted with 2 N methanolic ammonia

Sources & evidence

ORD record
ord-99c91517e4d7488f8b82006966a43a06
Source dataset
uspto-grants-2007_07
Patent number
US07244843B2

Reaction notes

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