Trifluoroacetic acid → Methyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-amine

HRID 2199198Notes

Reaction equation

HRID 2199198 reaction equation
C(O[C:6](=O)[N:7](C)[C:8]1[S:12][C:11]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[N:10][C:9]=1[C:19]([F:22])([F:21])[F:20])(C)(C)C.FC(F)(F)C(O)=O>ClCCCl>[CH3:6][NH:7][C:8]1[S:12][C:11]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[N:10][C:9]=1[C:19]([F:21])([F:20])[F:22]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66645247Methyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)carbamic acid tert-butyl ester

Product 1

HCID 59580723Methyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-amineYield 81%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of DCE (4 mL) was added methyl-(2-pyridin-3-yl-4-trifluoromethyl-thiazol-5-yl)-carbamic acid tert-butyl ester (0.616 g, 1.7 mmol) and trifluoroacetic acid (4 mL) and the mixture was stirred for 15 min. The solvents were removed under reduced pressure and the resulting residue was re-dissolved in DCE and aqueous saturated NaHCO3. The biphasic mixture was separated and the aqueous layer was extracted three times with DCE. The organic extracts were combined, dried over MgSO4, filtered and concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to give the desired product as an off-white solid (0.357 g, 80%): mp 152-157° C.; 1H NMR (300 MHz, CDCl3) δ 8.95 (d, J=2.3 Hz, 1H), 8.57 (dd, J=4.9, 1.7 Hz, 1H), 8.11 (dt, J=8.2, 2.3 Hz, 1H), 7.23 (ddd, J=7.9, 4.9, 0.7 Hz, 1H), 4.83 (br s, 1H), 3.05 (d, J=4.9 Hz, 3H); ESIMS m/z 260 (M+1), m/z 257.9 (M−1).

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe resulting residue was re-dissolved in DCE
  3. customThe biphasic mixture was separated
  4. extractionthe aqueous layer was extracted three times with DCE
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe crude product was purified by silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ebaae92632154b81b61c7b7b9c7a489d
Source dataset
uspto-grants-2016_06
Patent number
US09357780B2

Reaction notes

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