Tetrahydrofuran → 2-Amino-1-(6-(trifluoromethyl)pyridin-3-YL)ethanol

HRID 530615Notes

Reaction equation

HRID 530615 reaction equation
[N+:1]([CH2:4][CH:5]([C:7]1[CH:8]=[N:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=1)[OH:6])([O-])=O.C1COCC1.C([O-])=O.[NH4+]>[Pd].CO>[NH2:1][CH2:4][CH:5]([C:7]1[CH:8]=[N:9][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:11][CH:12]=1)[OH:6]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 67360344HCID 67360344, compound

Product 1

HCID 682416232-Amino-1-(6-(trifluoromethyl)pyridin-3-YL)ethanolYield 49.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

In a 250 mL round-bottomed flask, 2-nitro-1-(6-(trifluoromethyl)pyridin-3-yl)ethanol (2.4 g, 10.2 mmol) was combined with THF (40 ml) and methanol (40.0 ml) to give a colorless solution and placed under N2 atmosphere. 360 mg of 10% Pd/C was added. Ammonium formate (3.2 g, 50.8 mmol) was added. The reaction mixture was stirred at room temperature overnight. Complete by LCMS. The reaction mixture was purged with N2 and then filtered through Celite. The Celite filtercake was washed several times with methanol. The combined washes and filtrate was concentrated in vacuo. The residue was taken up in dichloromethane/0.01% NaOH and extracted 5 times with dichloromethane. The organic layers were dried over Na2SO4 and concentrated in vacuo. Product was still present in the aqueous phase so saturated NaCl was added to the aqueous phase and the aqueous phase was extracted 3 times with dichloromethane. The organic layers were dried over Na2SO4 and concentrated in vacuo. The combine product as a pale yellow solid was triturated with ether to get an off-white powder which was washed twice with ether/hexanes to afford 2-amino-1-(6-(trifluoromethyl)pyridin-3-yl)ethanol (1.05 g). (M+H)+=207 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.76 (dd, J=12.84, 7.93 Hz, 1H) 3.15 (dd, J=12.84, 3.78 Hz, 1H) 4.75 (dd, J=8.12, 3.97 Hz, 1H) 7.69 (d, J=8.31 Hz, 1H) 7.93 (dd, J=8.12, 1.70 Hz, 1H) 8.71 (d, J=1.51 Hz, 1H).

Workup

  1. customto give a colorless solution
  2. customThe reaction mixture was purged with N2
  3. filtrationfiltered through Celite
  4. washThe Celite filtercake was washed several times with methanol
  5. concentrationThe combined washes and filtrate was concentrated in vacuo
  6. extractionextracted 5 times with dichloromethane
  7. dry with materialThe organic layers were dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. additionwas added to the aqueous phase
  10. extractionthe aqueous phase was extracted 3 times with dichloromethane
  11. dry with materialThe organic layers were dried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe combine product as a pale yellow solid was triturated with ether
  14. customto get an off-white powder which
  15. washwas washed twice with ether/hexanes

Sources & evidence

ORD record
ord-01e9c9712c5a462e93f9a6a0dda68d68
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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