4-Aminopyridine → 4-(2,2,2-Trimethylacetamido)pyridine

HRID 2267315Notes

Reaction equation

HRID 2267315 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3](Cl)=[O:4].[NH2:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1.C(N(CC)CC)C>ClCCl>[N:12]1[CH:13]=[CH:14][C:9]([NH:8][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 17274-AminopyridineHCID 8471TriethylamineHCID 62493Pivaloyl chloride

Product 1

HCID 4270594-(2,2,2-Trimethylacetamido)pyridineYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of trimethylacetyl chloride (32.5 mL, 0.264 mol) in dry dichloromethane (50 mL) was added dropwise over 1 h to a stirred suspension of 4-aminopyridine (22.60 g, 0.240 mol) and triethylamine (41.8 mL, 0.300 mol) in dry dichloromethane (360 mL) at 0° C. under nitrogen. The ice bath was removed and the reaction allowed to warm to r.t. overnight. After 17 h, the pale brown mixture was poured into water (500 mL). The organic layer was separated and washed with a dilute aqueous solution of sodium hydrogen carbonate (400 mL). The organic layer was separated, dried over sodium sulfate, filtered and the solvent evaporated in vacuo. The crude solid was recrystallized from ethyl acetate (75 mL)/hexane (50 mL), washed with diethyl ether (2×10 mL) and air dried to yield N-(pyridin-4-yl)pivalamide (29.11 g, 68%) as colourless plate like crystals. 1H NMR: δ (CDCl3, 400 MHz) 1.33 (s, 9 H), 7.50 (d, J=6 Hz, 2 H), 7.56 (br. s., 1 H), 8.49 (d, J=6 Hz, 2 H).

Workup

  1. customThe ice bath was removed
  2. additionthe pale brown mixture was poured into water (500 mL)
  3. customThe organic layer was separated
  4. washwashed with a dilute aqueous solution of sodium hydrogen carbonate (400 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo
  9. customThe crude solid was recrystallized from ethyl acetate (75 mL)/hexane (50 mL)
  10. washwashed with diethyl ether (2×10 mL) and air
  11. customdried

Sources & evidence

ORD record
ord-8900c8d3bb4a4d2ca83dd87fe06aed36
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

Loading…