tert-Butanol → Trifluoroacetic acid

HRID 1521600Notes

Reaction equation

HRID 1521600 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[N:13][N:14]=[C:7]1[CH2:6][CH2:5]2.[CH3:15][C:16]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[N:28][CH:29]=1)([CH3:23])[CH2:17][O:18][C:19]([F:22])([F:21])[F:20].[C:33](=O)([O-:35])[O-:34].[K+].[K+].C(O)(C)(C)C>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O>[F:22][C:19]([F:20])([F:21])[C:33]([OH:35])=[O:34].[CH3:23][C:16]([C:24]1[CH:25]=[C:26]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]2[CH:12]=[N:13][N:14]=[C:7]2[CH2:6][CH2:5]3)[CH:27]=[N:28][CH:29]=1)([CH3:15])[CH2:17][O:18][C:19]([F:20])([F:21])[F:22]

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 21543699HCID 21543699, compoundHCID 709812375-(2-Methyl-1-(trifluoromethoxy)propan-2-yl)pyridin-3-ylboronic acid

Product 2

HCID 6422Trifluoroacetic acidHCID 665767717-{5-[2-Methyl-1-(trifluoromethoxy)-2-propanyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a vial containing the title compound from Example 22 Step B (50 mg, 0.200 mmol), the title compound from Example 64 Step C (63.1 mg, 0.240 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (28.3 mg, 0.040 mmol) and potassium carbonate (83 mg, 0.600 mmol) were added tert-butanol (2.2 mL) and water (0.28 mL). The vial was capped tightly and heated to 80° C. overnight. The reaction was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with acetonitrile and then purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid) to provide the title compound: LCMS m/z 389.00 [M+H]+; NMR (500 MHz, CD3OD) δ 9.99 (s, 1H), 9.19 (s, 1H), 9.02 (s, 1H), 8.94 (s, 1H), 8.09-8.00 (m, 3H), 4.33 (s, 2H), 3.48-3.45 (m, 2H), 3.39-3.36 (m, 2H), 1.60 (s, 6H).

Workup

  1. customThe vial was capped tightly
  2. temperatureThe reaction was then cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was diluted with acetonitrile
  5. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water

Sources & evidence

ORD record
ord-f14590fb1c4a4e0899a717956ae759aa
Source dataset
uspto-grants-2015_07
Patent number
US09073929B2

Reaction notes

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