Trifluoroacetic acid → HCID 76901514, compound

HRID 1174399Notes

Reaction equation

HRID 1174399 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:51]([CH3:55])([CH3:54])[CH2:52][OH:53])[C:10]([NH:12][C@@H:13]([CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C@@H:14]([OH:43])[CH2:15][C@@H:16]([NH:30][C:31](=[O:42])[C@H:32]([C:38]([CH3:41])([CH3:40])[CH3:39])[NH:33][C:34]([O:36][CH3:37])=[O:35])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[CH:20][CH:19]=1)=[O:11])=[O:7])(C)(C)C.FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C.ClC(OC)=O>ClCCl.O>[CH3:1][O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:51]([CH3:55])([CH3:54])[CH2:52][OH:53])[C:10](=[O:11])[NH:12][C@@H:13]([CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[C@@H:14]([OH:43])[CH2:15][C@H:16]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[CH:20][CH:19]=1)[NH:30][C:31](=[O:42])[C@H:32]([C:38]([CH3:41])([CH3:40])[CH3:39])[NH:33][C:34](=[O:35])[O:36][CH3:37]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 67406559HCID 67406559, compound

Product 1

HCID 76901514HCID 76901514, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Example 175A (0.025 mmol) in dichloromethane (1.0 mL) was added trifluoroacetic acid (1.0 mL), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated, and the reaction mixture was partitioned between ethyl acetate and dilute NaHCO3 solution. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was dissolved in tetrahydrofuran (0.25 mL) and diisopropylethylamine (0.015 mL, 0.086 mmol) and methyl chloroformate (0.002 mL, 0.026 mmol) were added at room temperature. After 2 hours water was added and the reaction was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with a gradient starting with dichloromethane and ending with ethyl acetate to give the title compound (0.006 g, 34% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.76 (2s, 6 H), 0.79 (s, 9 H), 1.45-1.56 (m, 2 H), 2.71-2.80 (m, 3 H), 3.08 (dd, J=5.4, 10.9 Hz, 1 H), 3.18 (dd, J=5.4, 10.9 Hz, 1 H), 3.49 (s, 3 H), 3.55 (s, 3 H), 3.59-3.67 (m, 1 H), 3.81 (d, J=9.6 Hz, 1 H), 4.02 (d, J=9.2 Hz, 1 H), 4.04-4.21 (m, 2 H), 4.62 (m, 1 H), 4.90 (d, J=5.5 Hz, 1 H), 6.61 (d, J=9.6 Hz, 1 H), 6.92 (d, J=9.2 Hz, 1 H), 7.10-7.21 (m, 7 H), 7.29-7.31 (m, 1 H), 7.47 (d, J=8.8 Hz, 1 H), 7.78 (d, J=8.8 Hz, 1 H), 7.82-7.89 (m, 4 H), 8.64 (m, 1 H).

Workup

  1. customThe solvent was evaporated
  2. customthe reaction mixture was partitioned between ethyl acetate and dilute NaHCO3 solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in tetrahydrofuran (0.25 mL)
  8. extractionthe reaction was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was chromatographed on silica gel eluting with a gradient

Sources & evidence

ORD record
ord-018dafa16fb74bfea83c0e41d74b8692
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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