Trifluoroacetic acid → benzyl (3R,8aS)-2,2-dimethyl-4-oxohexahydro-2H-pyrrolo[2,1-b][1,3]thiazin-3-ylcarbamate

HRID 529464Notes

Reaction equation

HRID 529464 reaction equation
C(O[CH:4](OCC)[CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:26])[C@@H:10]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:11]([SH:14])([CH3:13])[CH3:12])C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:12][C:11]1([CH3:13])[S:14][C@H:7]2[CH2:6][CH2:5][CH2:4][N:8]2[C:9](=[O:26])[C@H:10]1[NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86706198(R)-benzyl 1-(4,4-diethoxybutylamino)-3-mercapto-3-methyl-1-oxobutan-2-ylcarbamate

Product 1

HCID 68309771benzyl (3R,8aS)-2,2-dimethyl-4-oxohexahydro-2H-pyrrolo[2,1-b][1,3]thiazin-3-ylcarbamateYield 34.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a round bottom flask was added (R)-benzyl 1-(4,4-diethoxybutylamino)-3-mercapto-3-methyl-1-oxobutan-2-ylcarbamate (6.90 g, 16.2 mmol), DCM (50 mL) and TFA (1.87 mL, 24.3 mmol). The reaction was stirred at rt for 5 hr. The reaction was diluted with DCM (200 mL) and the organics was washed with saturated aqueous NaHCO3 (200 mL), water (200 mL) and saturated aqueous NaCl (200 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give benzyl (3R,8aS)-2,2-dimethyl-4-oxohexahydro-2H-pyrrolo[2,1-b][1,3]thiazin-3-ylcarbamate (1.89 g, 5.65 mmol, 34.9% yield) as a clear oil. Anal. Calcd. for C12H22N2O3S m/z 334.3. found: 335.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.29-7.44 (m, 5H), 5.92 (d, J=7.15 Hz, 1H), 5.14 (s, 3H), 4.57 (d, J=7.70 Hz, 1H), 3.89-3.68 (m, 1H), 3.60-3.40 (m, 1H), 2.55-2.34 (m, 1H), 2.18-2.00 (m, 1H), 1.99-1.83 (m, 2H), 1.51 (s, 3H), 1.13 (s, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 167.31, 157.00, 136.19, 128.54, 128.20, 128.08, 67.23, 60.46, 55.12, 48.93, 46.26, 33.10, 29.56, 27.70, 23.39.

Workup

  1. washthe organics was washed with saturated aqueous NaHCO3 (200 mL), water (200 mL) and saturated aqueous NaCl (200 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified
  7. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-0a6f5f1c70914509ac2a93520777c42d
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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