Trifluoroacetic acid → HCID 73054853, compound

HRID 1055453Notes

Reaction equation

HRID 1055453 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][O:9][C:10](=[O:61])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19]([C:21]2[C:31]3[O:30][CH2:29][C@H:28]([NH:32][C:33](=[O:45])[C@@H:34]([N:36](C(OC(C)(C)C)=O)[CH3:37])[CH3:35])[C:27](=[O:46])[N:26]([CH2:47][C:48]4[C:57]5[C:52](=[CH:53][C:54]([Br:58])=[CH:55][CH:56]=5)[CH:51]=[CH:50][C:49]=4[O:59][CH3:60])[C:25]=3[CH:24]=[CH:23][CH:22]=2)=[O:20])=[CH:13][CH:12]=1>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:61])[C:11]1[CH:12]=[CH:13][C:14]([CH2:17][NH:18][C:19]([C:21]2[C:31]3[O:30][CH2:29][C@H:28]([NH:32][C:33](=[O:45])[C@@H:34]([NH:36][CH3:37])[CH3:35])[C:27](=[O:46])[N:26]([CH2:47][C:48]4[C:57]5[C:52](=[CH:53][C:54]([Br:58])=[CH:55][CH:56]=5)[CH:51]=[CH:50][C:49]=4[O:59][CH3:60])[C:25]=3[CH:24]=[CH:23][CH:22]=2)=[O:20])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90037524HCID 90037524, compound

Product 1

HCID 73054853HCID 73054853, compoundYield 95.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (340 mg, 222 μl, 2.99 mmol, Eq: 200.00) was added to a solution of 4-[({(S)-9-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-7-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionyl amino]-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocycloheptene-4-carbonyl}-amino)-methyl]-benzoic acid methyl ester (12 mg, 14.9 μmol, Eq: 1.00) in DCM (300 μl) at 0° C. After 1 h the mixture was concentrated and the residue dissolved in DCM. The solution was washed with sat. NaHCO3 and the NaHCO3 solution back extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered and concentrated. The residue was dissolved in a minimum of DCM. Et2O was added followed by pentane which resulted in a precipitate. The supernatant was decanted, the residue was washed with pentane and dried in vacuo to afford the title compound (10 mg, 95%) as a white solid. 1H NMR (DMSO-d6) δ: 8.81 (br. s., 1H), 8.22 (d, J=8.2 Hz, 1H), 8.03-8.12 (m, 2H), 7.87 (d, J=8.5 Hz, 2H), 7.79 (d, J=9.1 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.53 (dd, J=9.2, 2.0 Hz, 1H), 7.32-7.40 (m, 3H), 7.25-7.31 (m, 1H), 7.16-7.25 (m, 1H), 5.87 (d, J=14.8 Hz, 1H), 5.24 (d, J=14.8 Hz, 1H), 4.66-4.82 (m, 1H), 4.13-4.52 (m, 4H), 3.78 (s, 3H), 2.94 (d, J=6.9 Hz, 1H), 2.20 (s, 3H), 1.08 (d, J=6.9 Hz, 3H)

Workup

  1. concentrationAfter 1 h the mixture was concentrated
  2. dissolutionthe residue dissolved in DCM
  3. washThe solution was washed with sat. NaHCO3
  4. extractionthe NaHCO3 solution back extracted with DCM
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in a minimum of DCM
  9. additionEt2O was added
  10. customresulted in a precipitate
  11. customThe supernatant was decanted
  12. washthe residue was washed with pentane
  13. customdried in vacuo

Sources & evidence

ORD record
ord-b1dc0c2efc7947749614f1d1bace80dd
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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