Trifluoroacetic acid → 4-(Difluoromethyl)pyridin-2-amine

HRID 1057036Notes

Reaction equation

HRID 1057036 reaction equation
C([NH:5][C:6]1[CH:11]=[C:10]([CH:12]([F:14])[F:13])[CH:9]=[CH:8][N:7]=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>>[F:13][CH:12]([F:14])[C:10]1[CH:9]=[CH:8][N:7]=[C:6]([NH2:5])[CH:11]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 90015299N-tert-butyl-4-(difluoromethyl)pyridin-2-amine

Product 1

HCID 672825704-(Difluoromethyl)pyridin-2-amineYield 99.2%

Conditions

Temperature
90 °C

Procedure

A flask containing N-tert-butyl-4-(difluoromethyl)pyridin-2-amine (4.43 g, 22.1 mmol), triethylsilane (7.28 mL, 44.2 mmol) and trifluoroacetic acid (22.1 mL, 1 M) was fitted with a reflux condenser. The reaction mixture was stirred at 90° C. for 21 hr and then, after cooling to rt, concentrated to dryness and partitioned between CH2Cl2 and sat. aq. NaHCO3. After separation of the phases, the aqueous layer was re-extracted with CH2Cl2 and the combined organics were dried over MgSO4. Concentration afforded 4-(difluoromethyl)pyridin-2-amine as a light brown solid (3.16 g, >99%); 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=5.3 Hz, 1H), 6.74 (d, J=5.3 Hz, 1H), 6.66-6.33 (m, 2H), 4.62 (br s, 2H).

Workup

  1. customwas fitted with a reflux condenser
  2. temperatureafter cooling to rt
  3. concentrationconcentrated to dryness
  4. custompartitioned between CH2Cl2 and sat. aq. NaHCO3
  5. customAfter separation of the phases
  6. extractionthe aqueous layer was re-extracted with CH2Cl2
  7. dry with materialthe combined organics were dried over MgSO4
  8. concentrationConcentration

Sources & evidence

ORD record
ord-1351daa0380c4760913980a072d33aef
Source dataset
uspto-grants-2016_07
Patent number
US09399636B2

Reaction notes

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