Trifluoroacetic acid → 3-(pyridin-3-yl)prop-2-yn-1-amine

HRID 1913367Notes

Reaction equation

HRID 1913367 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]#[C:8][CH2:9][NH:10]C(=O)OC(C)(C)C)[CH:2]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]#[C:8][CH2:9][NH2:10])[CH:2]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 70832777tert-Butyl [3-(pyridin-3-yl)prop-2-yn-1-yl]carbamate

Product 1

HCID 112635103-(pyridin-3-yl)prop-2-yn-1-amineYield 97.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 47 (104 mg, 0.45 mmol) in CH2Cl2 (1 mL) was added TFA (2 mL, excess) and the resultant solution was stirred at room temperature for 1 h. The solvent and excess TFA were removed under a stream of nitrogen and the residue was partitioned between HCl(aq) (1.0 M, 2 mL) and EtOAc (10 mL). The aqueous fraction was collected and subsequently washed with EtOAc (2×10 mL). To the remaining aqueous fraction was added CH2Cl2 (20 mL) and water (20 mL) and the pH was adjusted to 10 with NaOH(aq) (10 N) while stirring. The organic fraction was collected and the remaining aqueous fraction was extracted with CH2Cl2 (2×15 mL). The combined organic fractions were dried (Na2SO4), filtered and the solvent was removed in vacuo to afford the title compound 48 (free base, 58 mg, 97% yield) as a brown oil. Due to the high potential of autooxidation, the dihydrochloride salt was made by dissolving the amine free base in Et2O and precipitating with etherial HCl. The solvent and excess HCl were removed in vacuo, the solid dihydrochloride was triturated with Et2O and collected by filtration to afford the title compound 48 (dihydrochloride, 91 mg, 99% yield) as a white solid: 1H NMR (D2O) δ 8.94 (m, 1H), 8.79 (m, 1H), 8.65 (m, 1H), 8.06 (m, 1H), 4.15 (s, 2H); LRMS (ESI) m/z calcd for C8H9N2 [M+H]+ 133. found 133; HRMS (ESI) m/z calcd for C8H9N2 [M+H]+ 133.0766. found 133.0763; HPLC>98% (tR=5.70 min, 60 (A):40 (B): 0.02 (C); tR=3.05 min, 60 (A):40 (B): 0.07 (C)).

Workup

  1. customThe solvent and excess TFA were removed under a stream of nitrogen
  2. customthe residue was partitioned between HCl(aq) (1.0 M, 2 mL) and EtOAc (10 mL)
  3. customThe aqueous fraction was collected
  4. washsubsequently washed with EtOAc (2×10 mL)
  5. additionTo the remaining aqueous fraction was added CH2Cl2 (20 mL) and water (20 mL)
  6. customThe organic fraction was collected
  7. extractionthe remaining aqueous fraction was extracted with CH2Cl2 (2×15 mL)
  8. dry with materialThe combined organic fractions were dried (Na2SO4)
  9. filtrationfiltered
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-cbeeae8e70604944a16b8b0285ff80d6
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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