Hydrochloric Acid → Trifluoroacetic acid

HRID 1891212Notes

Reaction equation

HRID 1891212 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][CH:9]([C:12]3[CH:46]=[CH:45][C:15]([CH2:16][O:17][C:18]4[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=4[C:25]4[N:30]=[C:29]([N:31]5[C:35]([C:36]([F:39])([F:38])[F:37])=[C:34]([C:40]([O:42]CC)=[O:41])[CH:33]=[N:32]5)[CH:28]=[CH:27][CH:26]=4)=[CH:14][CH:13]=3)[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[OH-:47].[Li+].Cl.[O:50]1CCOCC1>>[C:35]([OH:50])([C:36]([F:39])([F:38])[F:37])=[O:47].[CH:1]1([C:4]([N:6]2[CH2:7][CH2:8][CH:9]([C:12]3[CH:13]=[CH:14][C:15]([CH2:16][O:17][C:18]4[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=4[C:25]4[N:30]=[C:29]([N:31]5[C:35]([C:36]([F:39])([F:38])[F:37])=[C:34]([C:40]([OH:42])=[O:41])[CH:33]=[N:32]5)[CH:28]=[CH:27][CH:26]=4)=[CH:45][CH:46]=3)[CH2:10][CH2:11]2)=[O:5])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 68488744HCID 68488744, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 59451992HCID 59451992, compound

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 6 Step A (44 mg, 0.07 mmol) in 1,4-dioxane (2 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 2 h, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid (1.5 mL), then was diluted with 1,4-dioxane and passed though a 0.45 micron syringe filter. Purification by reverse phase HPLC (40 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 608.9 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.33 (s, 1H), 8.15 (t, J=8.0 Hz, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.45-7.41 (m, 1H), 7.27 (ddd, J=8.0, 8.0, 4JH-F=5.5 Hz, 1H), 7.08 (dd, J=16.5, 8.0 Hz, 4H), 4.95 (s, 2H), 4.56-4.30 (m, 2H), 3.22-3.04 (m, 1H), 2.78-2.68 (m, 1H), 2.68-2.56 (m, 1H), 2.24-1.94 (m, 1H), 1.82-1.62 (br m, 2H), 1.56-1.30 (br m, 2H), 0.82-0.64 (m, 4H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (40 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-0a8006ba49364b14a393a918c9155684
Source dataset
uspto-grants-2013_08
Patent number
US08507512B2

Reaction notes

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