Hydrochloric Acid → 1-Cyclohexyl-3-ethyl-6-fluoro-1H-indazole

HRID 1936738

Reaction equation

HRID 1936738 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10][CH3:11].C([O-])(=O)C.[Na+].S(O)(=O)(=O)C.[CH:23]1([NH:29][NH2:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.Cl>C1(C)C=CC=CC=1>[CH:23]1([N:29]2[C:2]3[C:3](=[CH:4][CH:5]=[C:6]([F:8])[CH:7]=3)[C:9]([CH2:10][CH3:11])=[N:30]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1235862',4'-DifluoropropiophenoneHCID 517045Sodium AcetateHCID 22009940Cyclohexylhydrazine mesylate

Product 1

HCID 98596991-Cyclohexyl-3-ethyl-6-fluoro-1H-indazoleYield 98%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1-(2,4-difluoro-phenyl)-propan-1-one (21.29 g, 125.1 mmol) in toluene (120 mL) was added sodium acetate (26.75 g, 326.1 mmol) and cyclohexylhydrazine mesylate (34.0 g, 163 mmol). The reaction mixture was heated to reflux in a Dean-Stark apparatus for 12 hours. The reaction was cooled to room temperature and poured into 1 N hydrochloric acid (100 mL). The toluene layer was separated and washed with water (75 mL) and brine (75 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield 30.07 g of 1-cyclohexyl-3-ethyl-6-fluoro-1H-indazole (98% yield). 1H NMR (400 MHz, CDCl3) d 1.33 (t, 3, J=7.7), 1.35-1.44 (m, 2), 1.47-1.96 (m, 8), 2.93 (q, 2, J=7.7), 4.14-4.22 (m1), 6.81 (dt, 1, J=8.9, 2.1), 6.99 (dd, 1, J=9.8, 2.1), 7.40 (ddd, 1, J=8.7, 5.2, 0.4). 13C NMR (100 MHz, CDCl3) d 13.97, 20.53, 25.37, 25.84, 32.32, 58.18, 94.77 (d, J=27.4), 109.11 (d, J=26.0), 119.38, 121.75 (d, J=11.5), 139.89 (d, J=13.0), 146.61, 161.95 (d, J=242). IR 2968, 2934, 2856, 1624, 1507, 1174, 1125, 825 cm−1. Analysis calculated for C15H19FN2: C, 73.14; H, 7.77; N, 11.37. Found: C, 73.33; H, 7.90; N, 11.46.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux in a Dean-Stark apparatus for 12 hours
  3. customThe toluene layer was separated
  4. washwashed with water (75 mL) and brine (75 mL)
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ff887e33ecaa4f0c9560bbb4843e6412
Source dataset
uspto-grants-2002_05
Patent number
US06391872B1

Linked notes

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