Phenol → Methyl 2-(phenoxymethyl)isonicotinate

HRID 1963242Notes

Reaction equation

HRID 1963242 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][N:12]=1)[C:6]([O:8][CH3:9])=[O:7].[C:13]1(O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O>C1COCC1>[O:1]([CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][N:12]=1)[C:6]([O:8][CH3:9])=[O:7])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 13276248Methyl 2-(hydroxymethyl)pyridine-4-carboxylate

Product 1

HCID 59536560Methyl 2-(phenoxymethyl)isonicotinateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-(hydroxymethyl)isonicotinate (2.232 g, 13.35 mmol) dissolved in THF (15 mL) and phenol (1.426 mL, 16.02 mmol) and triphenylphosphine (3.71 mL, 16.02 mmol) were added. The mixture was cooled to 0° C. (E)-diisopropyl diazene-1,2-dicarboxylate (3.24 g, 16.02 mmol) was added dropwise, the ice-bath removed and the reaction stirred at room temperature for 2 h. The solvent was evaporated and the residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. 4:1 of EtOAc in heptane over 10 CV was used as mobile phase. Methyl 2-(phenoxymethyl)isonicotinate (2.65 g, 82%) was isolated. 1H NMR (400 MHz, cdcl3) δ 3.96 (s, 3H), 5.26 (s, 2H), 6.95-7.04 (m, 3H), 7.27-7.34 (m, 2H), 7.76-7.80 (m, 1H), 8.10 (s, 1H), 8.75 (d, 1H). MS m/z 244 (M+H)+

Workup

  1. additionwas added dropwise
  2. customthe ice-bath removed
  3. customThe solvent was evaporated
  4. customthe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column

Sources & evidence

ORD record
ord-35395e27d41d40c7881dc13141bfe43a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…