Trifluoroacetic acid → HCID 57910774, compound

HRID 1644865Notes

Reaction equation

HRID 1644865 reaction equation
Cl[C:2](=[N:8][OH:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].CO[C:12]([C:14]1[CH:19]=[CH:18][C:17]([C:20]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)=[CH:27][N:26]=2)([CH3:24])[CH:21]([CH3:23])[CH3:22])=[CH:16][CH:15]=1)=[CH2:13].C(N(CC)CC)C.C(O)(C(F)(F)F)=O>C1COCC1>[CH3:24][C:20]([C:17]1[CH:16]=[CH:15][C:14]([C:12]2[O:9][N:8]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:13]=2)=[CH:19][CH:18]=1)([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[CH:27][N:26]=1)[CH:21]([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 6816376Ethyl chloro(hydroximino)acetateHCID 57910788HCID 57910788, compound2×

Product 1

HCID 57910774HCID 57910774, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-chloro-2-(hydroxyimino)acetate (3.15 g, 20.7 mmol) was added to a stirred solution of 1b (crude product from Step B; 6.91 mmol) and triethylamine (9.60 mL, 69.1 mmol) in THF (100 mL) at rt. After approximately 1 h, the reaction mixture was acidified to pH ˜1 by the addition of TFA, and the resulting mixture was heated to 50° C. After 1 h, the reaction mixture was concentrated in vacuo, the residue redissolved in TFA (30 mL) and the resulting solution was heated to 50° C. for an additional 1 h. After evaporation of the volatiles in vacuo, the crude residue was dissolved in EtOAc and carefully neutralized by the addition of saturated aqueous sodium bicarbonate. The organic layer was separated, dried (sodium sulfate), concentrated in vacuo, and the resulting crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-100% EtOAc/hexanes as eluent) to afford the title compound 1c. m/z (ES) 472 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.61 (d, 1H, J=3.5 Hz), 8.40 (d, 1H, J=2.2 Hz), 7.77 (m, 1H), 7.70 (d, 2H, J=8.5 Hz), 7.55 (d, 1H, J=7.7 Hz), 7.49 (d, 2H, J=8.4 Hz), 7.20 (m, 3H), 6.87 (s, 1H), 5.24 (s, 2H), 4.48 (q, 2H, J=7.1 Hz), 3.11 (m, 1H, J=6.6 Hz), 1.70 (s, 3H), 1.46 (t, 3H, J=7.1 Hz), 0.87 (d, 3H, J=6.7 Hz), 0.80 (d, 3H, J=6.9 Hz).

Workup

  1. waitAfter 1 h
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue redissolved in TFA (30 mL)
  4. temperaturethe resulting solution was heated to 50° C. for an additional 1 h
  5. customAfter evaporation of the volatiles in vacuo
  6. dissolutionthe crude residue was dissolved in EtOAc
  7. additioncarefully neutralized by the addition of saturated aqueous sodium bicarbonate
  8. customThe organic layer was separated
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. customthe resulting crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-100% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-aba7b3356b8d41c0851c8297c6f24df2
Source dataset
uspto-grants-2012_02
Patent number
US08124628B2

Reaction notes

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