Trifluoroacetic acid → HCID 66699272, compound

HRID 2092134Notes

Reaction equation

HRID 2092134 reaction equation
Cl[C:2](=[N:8][OH:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([C:29]3[CH:34]=[CH:33][C:32]([C:35](OC)=[CH2:36])=[CH:31][N:30]=3)([CH3:28])[CH:25]([CH3:27])[CH3:26])=[CH:20][CH:19]=2)[CH:15]=[N:16][CH:17]=1.C(N(CC)CC)C.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([C:18]2[CH:19]=[CH:20][C:21]([C:24]([C:29]3[N:30]=[CH:31][C:32]([C:35]4[O:9][N:8]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:36]=4)=[CH:33][CH:34]=3)([CH3:28])[CH:25]([CH3:26])[CH3:27])=[CH:22][CH:23]=2)[CH:15]=[N:16][CH:17]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 6816376Ethyl chloro(hydroximino)acetateHCID 59393670HCID 59393670, compound

Product 1

HCID 66699272HCID 66699272, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-chloro-2-(hydroxyimino)acetate (116 mg, 0.768 mmol) was added to a stirred solution of 3a (0.256 mmol) and triethylamine (357 μL, 2.56 mmol) in THF (10.0 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. for approximately 4.5 h. The reaction mixture was cooled to rt, neutralized with saturated aqueous sodium bicarbonate and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-100% EtOAc/hexanes as eluent) to afford the title compound 3b. m/z (ES) 472 (MH)+. 1HNMR (500 MHz, CDCl3): δ 9.05 (d, 1H, J=2.3 Hz), 8.46 (d, 1H, J=2.4 Hz), 8.29 (d, 1H, J=2.5 Hz), 8.00 (dd, 1H, J=2.3, 8.5 Hz), 7.51 (m, 4H), 7.41 (d, 1H, J=8.2 Hz), 7.36 (m, 1H), 6.98 (s, 1H), 4.50 (q, 2H, J=7.1 Hz), 3.92 (s, 3H), 3.71 (m, 1H), 1.78 (s, 1H), 1.47 (t, 3H, J=7.1 Hz), 0.91 (d, 3H, J=6.7 Hz), 0.88 (d, 3H, J=6.9 Hz).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated in vacuo
  3. customThe crude residue was purified by flash chromatography on silica gel (gradient elution; 0%-100% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-f872ea7de6d04fe08e5c2b66be252238
Source dataset
uspto-grants-2013_05
Patent number
US08440672B2

Reaction notes

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