Trifluoroacetic acid → Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

HRID 2364128Notes

Reaction equation

HRID 2364128 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][C:7]2[CH:8]=[C:9]([NH:16]C(OC(C)(C)C)=O)[C:10]([C:13]([O-:15])=[O:14])=[N:11][CH:12]=2)=[CH:4][CH:3]=1.F[C:27](F)(F)[C:28](O)=O>C(Cl)Cl>[NH2:16][C:9]1[C:10]([C:13]([O:15][CH2:27][CH3:28])=[O:14])=[N:11][CH:12]=[C:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:25][CH:24]=2)[CH:8]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866228435-(4-Fluorobenzyl)-3-[(tert-butoxy)carbonyl]amino-2-pyridinecarboxylate

Product 1

HCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-(4-fluorobenzyl)-3-[(tert-butoxy)carbonyl]amino-2-pyridinecarboxylate (29 g, 77 mmol) in CH2Cl2 (200 mL) and trifluoroacetic acid (60 mL) was stirred at rt overnight. The solvent was removed in vacuo and the crude material was dissolved in EtOAc and washed with NaHCO3 solution and brine. The organic layer was dried, concentrated and chromatographed on silica gel eluting with 20-60% EtOAc/hexanes to yield the product as a light yellow solid: 1H NMR (d6-DMSO) δ 7.76 (1H, d, J=1.7 Hz), 7.25 (2H, m), 7.15 (2H, t, J=9 Hz), 6.92 (1H, d,J=1.7 Hz), 6.62 (2H, br s), 4.23 (2H, q, J=7 Hz), 3.87 (2H, s), 1.26 (3H, t, J=7 Hz), AP+ MS: 275 (M+H+, 100); HRMS calcd for C15H15FN2O2+H+: 275.1196. Found: 275.1206.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe crude material was dissolved in EtOAc
  3. washwashed with NaHCO3 solution and brine
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customchromatographed on silica gel eluting with 20-60% EtOAc/hexanes

Sources & evidence

ORD record
ord-785a6cdc8e254678bb9582369aa64494
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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