Hydrochloric Acid → Trifluoroacetic acid

HRID 1255172Notes

Reaction equation

HRID 1255172 reaction equation
[F:1][C:2]([F:46])([F:45])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][O:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)=[CH:24][CH:23]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:40]([O:42]CC)=[O:41].[OH-:47].[Li+].Cl.[O:50]1CCOCC1>>[C:3]([OH:50])([C:2]([F:46])([F:45])[F:1])=[O:47].[F:46][C:2]([F:1])([F:45])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([CH2:28][O:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)=[CH:26][CH:27]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:40]([OH:42])=[O:41]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 86633491HCID 86633491, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 25233298HCID 25233298, compound

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 7 Step B (15.0 mg, 0.023 mmol) 1,4-dioxane (0.500 mL) was added lithium hydroxide (0.5 mL, 2.0 M in water, 1.00 mmol), and the resulting mixture was stirred at 50° C. After 30 min, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (30 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 614.2 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.29 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.10 (t, J=8.0 Hz, 1H), 7.73 (dd, J=7.5, 1.5 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.65 (d, J=8.5 Hz, 2H), 7.46-7.41 (m, 5H), 7.27 (d, J=8.5 Hz, 1H), 7.18 (d, J=8.5 Hz, 2H), 7.09 (t, J=7.5 Hz, 1H), 5.25 (s, 2H), 5.18 (s, 2H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (30 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-55f46761d1a14d999236e22f4e46ee56
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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