Trifluoroacetic acid → 4-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3-hydroxy-butyryl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

HRID 1949631Notes

Reaction equation

HRID 1949631 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([C:16]2[C:24]3[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[CH:13]2[N:26]([C:29](=[O:55])[CH:30]([NH:38][C:39](=[O:54])[CH:40]([N:42]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[CH3:43])[CH3:41])[CH:31]([O:33]C(C)(C)C)[CH3:32])[CH2:27][CH2:28][CH:12]12)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([C:16]2[C:24]3[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[CH:13]2[N:26]([C:29](=[O:55])[CH:30]([NH:38][C:39](=[O:54])[CH:40]([N:42]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[CH3:43])[CH3:41])[CH:31]([OH:33])[CH3:32])[CH2:27][CH2:28][CH:12]12)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674091784-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3-tert-butoxy-butyryl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

Product 1

HCID 674108714-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3-hydroxy-butyryl}-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl esterYield 97.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution containing crude 45 (330 mg, 0.44 mmol) in DCM (10 mL) was treated with TFA (3 mL) at ambient temperature. After 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc and the resultant organic solution was washed successively with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 300 mg of 46 as a pale brown-colored foam which was used without further purification. 1H NMR (CDCl3, 300 MHz) mixture of rotamers: δ8.38 (s, 0.5H), 8.34 (s, 0.5H), 8.12 (dd, J=5.1, 8.7 Hz, 0.5H), 8.03 (dd, J=5.4, 8.4 Hz, 0.5H), 7.35-7.26 (m, 5H), 7.05-6.87 (m, 2H), 6.77 (s, 0.5H), 6.62 (s, 0.5H), 5.29-5.12 (m, 3H), 4.76-4.52 (m, 1.5H), 4.34-4.30 (m, 1H), 4.22-4.19 (m, 0.5H), 3.89 (app t, J=5.4 Hz, 1H), 3.57-3.42 (m, 2H), 2.82 (s, 3H), 2.45-2.39 (m, 0.5H), 2.27-2.21 (m, 0.5H), 1.90 (br s, 1H), 1.38 (d, J=7.5 Hz, 3H), 1.16 (d, J=6.3 Hz, 3H) ppm. Mass spectrum, m/z [700.3] (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc
  3. washthe resultant organic solution was washed successively with saturated aqueous NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4dd89d0dd5b544a1a916bbf4e09a609a
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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