Trifluoroacetic acid → HCID 131730610, compound

HRID 1253956Notes

Reaction equation

HRID 1253956 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][O:8][CH3:9].[CH2:10]1[O:18][C:17]2[C:12](=[C:13]([S:19]([NH:22]C(OC(C)(C)C)=O)(=[O:21])=[O:20])[CH:14]=[CH:15][CH:16]=2)[O:11]1.FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][O:8][CH3:9].[CH2:10]1[O:18][C:17]2[C:12](=[C:13]([S:19]([NH2:22])(=[O:20])=[O:21])[CH:14]=[CH:15][CH:16]=2)[O:11]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 131730611HCID 131730611, compound

Product 1

HCID 131730610HCID 131730610, compoundYield 199.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boc methylenedioxybenzenesulfonamide bis-methoxyethylamine tethered product (18) (0.023 g, 0.033 mmol) was dissolved in DCM (1 mL). Trifluoroacetic acid (0.5 mL) was added dropwise, and the reaction was stirred at room temperature for 1 hour. The solvent was removed in vacuo, and the resultant orange oil was dissolved in DCM (1 mL) and the solution cooled to 0° C. using an ice bath. Diisopropylethylamine (0.173 mL, 0.99 mmol) was added dropwise with stirring, followed by (3R,3aS,6aR) hexahydrofuro[2,3-b]furan-2-yl 4-nitrophenyl carbonate (0.012 g, 0.040 mmol) in one portion as a solid. After 5 minutes, the ice bath was removed and the reaction mixture was allowed to warm to room temperature with stirring overnight. The solvent was removed in vacuo, and the resultant yellow oil was purified by flash column:chromatography (4:1 ethyl acetate/hexane to ethyl acetate to 9:1 DCM/methanol) to give bis-THE methylenedioxybenzenesulfonamide bis-methoxyethylamine tethered product (51) (0.022 g, 89%) as a yellow foam: Rf=0.50 (9:1 DCM/methanol); 1H NMR (CDCl3): 7.33 (1H, dd, J=8.2, 1.8 Hz), 7.17 (1H, d, J=1.8 Hz), 7.13 (2H, d, J=8.6 Hz) 6.89 (1H, d, J=8.2 Hz), 6.80 (2H, d, J=8.6 Hz), 6.09 (2H, s), 5.65 (1H, 8, J=5.2 Hz), 5.08-4.98 (2H, m), 4.35-4.24 (2H, m), 4.00-3.90 (1H, m), 3.90-3.63 (6H, m), 3.61-3.49 (2H, m), 3.42-3.31 (2H, m), 3.35 (6H, s), 3.16-3.07 (2H, m), 3.05-2.88 (4H, m), 2.88-2.74 (2H, m), 1.83 (1H; septet, J=6.6 Hz), 1.74-1.54 (1H, m), 1.48-1.35 (5H, m); 0.92 (3H, d, J=6.6 Hz), 0.88 (3H, d, J=6.6 Hz), OH signal not observed; coupled LCMS showed the product as a single major peak with m/z 752 [M+H]+; HPLC (205 nm) showed the material as a single major peak at RT of 1.92 min. (purity=91%).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe resultant orange oil was dissolved in DCM (1 mL)
  3. temperaturethe solution cooled to 0° C.
  4. stirringwith stirring
  5. waitAfter 5 minutes
  6. customthe ice bath was removed
  7. temperatureto warm to room temperature
  8. stirringwith stirring overnight
  9. customThe solvent was removed in vacuo
  10. customthe resultant yellow oil was purified by flash column

Sources & evidence

ORD record
ord-9d5979087f6c41ce8a73209bfc1843ff
Source dataset
uspto-grants-2013_06
Patent number
US08455497B2

Reaction notes

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