Hydrochloric Acid → Trifluoroacetic acid

HRID 1255183Notes

Reaction equation

HRID 1255183 reaction equation
[F:1][C:2]1([F:42])[CH2:7][CH2:6][CH:5]([C:8]2[CH:41]=[CH:40][C:11]([CH2:12][O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[N:25]=[C:24]([N:26]4[C:30]([C:31]([F:34])([F:33])[F:32])=[C:29]([C:35]([O:37]CC)=[O:36])[CH:28]=[N:27]4)[CH:23]=[CH:22][CH:21]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[OH-:43].[Li+].Cl.[O:46]1CCOCC1>>[C:30]([OH:46])([C:31]([F:34])([F:33])[F:32])=[O:43].[F:42][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([C:8]2[CH:41]=[CH:40][C:11]([CH2:12][O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[N:25]=[C:24]([N:26]4[C:30]([C:31]([F:33])([F:34])[F:32])=[C:29]([C:35]([OH:37])=[O:36])[CH:28]=[N:27]4)[CH:23]=[CH:22][CH:21]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 67159240HCID 67159240, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 25233640HCID 25233640, compound

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 11 Step A (20.0 mg, 0.034 mmol) in 1,4-dioxane (1 mL) was added lithium hydroxide (0.500 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 (50 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 558.2 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.29 (s, 1H), 8.15-8.09 (m, 2H), 7.73 (dd, J=8.0, 1.5 Hz, 1H), 7.70 (d, J=7.0 Hz, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.35 (d, J=7.0 Hz, 2H), 7.27 (d, J=8.5 Hz, 1H), 7.23 (d, J=7.0 Hz, 2H), 7.09 (t, J=8.5 Hz, 1H), 5.20 (s, 2H), 2.71-2.66 (m, 1H), 2.11-2.07 (m, 2H), 2.00-1.83 (m, 4H), 1.67-1.60 (m, 2H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (50 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-ce929d49413247a4866e28ecb759d15a
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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