Trifluoroacetic acid → benzyl (4S,10aS)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

HRID 529498Notes

Reaction equation

HRID 529498 reaction equation
[SH:1][CH2:2][CH2:3][C@H:4]([NH:14][C:15](=[O:24])[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:5](=[O:13])[NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:13]=[C:5]1[C@@H:4]([NH:14][C:15](=[O:24])[O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:3][CH2:2][S:1][C@H:7]2[CH2:8][CH2:9][CH2:10][CH2:11][N:6]12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86706211(S)-benzyl 4-mercapto-1-oxo-1-(5-oxopentylamino)butan-2-ylcarbamate

Product 1

HCID 86706212benzyl (4S,10aS)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-benzyl 4-mercapto-1-oxo-1-(5-oxopentylamino)butan-2-ylcarbamate (150 mg, 0.426 mmol) in DCM (5 mL) at rt was added a couple drops of TFA (by pipette). The mixture was stirred at 50° C. (gentle refluxing) for 1.5 hr. The reaction mixture was cooled to rt and concentrated. The residue was diluted with EtOAc. The EtOAc solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl (2×), dried over Na2SO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-70% EtOAc/Hex to give benzyl (4S,10aS)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (115 mg, 0.344 mmol, 81% yield). Anal. Calcd. for C12H22N2O3S m/z 334.3. found: 335.3 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.43-7.26 (m, 5H), 6.25 (d, J=6.5 Hz, 1H), 5.28 (dd, J=7.7, 3.0 Hz, 1H), 5.10 (d, J=2.5 Hz, 2H), 4.86 (ddd, J=10.3, 6.8, 3.3 Hz, 1H), 4.28 (d, J=13.8 Hz, 1H), 3.19 (ddd, J=14.1, 11.0, 2.7 Hz, 1H), 3.07-2.87 (m, 1H), 2.70 (ddd, J=14.4, 6.1, 3.0 Hz, 1H), 2.44-2.25 (m, 1H), 2.06-1.89 (m, 2H), 1.86-1.60 (m, 3H), 1.60-1.39 (m, 2H).

Workup

  1. temperature(gentle refluxing) for 1.5 hr
  2. temperatureThe reaction mixture was cooled to rt
  3. concentrationconcentrated
  4. additionThe residue was diluted with EtOAc
  5. washThe EtOAc solution was washed with saturated aqueous NaHCO3, saturated aqueous NaCl (2×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified
  10. washeluting with a gradient of 0-70% EtOAc/Hex

Sources & evidence

ORD record
ord-5deff966c85d418cacac9366f6a40201
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

Loading…