Methyl Glycolate → [5-(4-Fluorophenylcarbamoyl)Pyridin-2-Yloxy]Acetic Acid Methyl Ester

HRID 859165Notes

Reaction equation

HRID 859165 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[C:18]([O:22][CH3:23])(=[O:21])[CH2:19][OH:20].CC(C)([O-])C.[K+]>C1COCC1>[CH3:23][O:22][C:18](=[O:21])[CH2:19][O:20][C:2]1[CH:17]=[CH:16][C:5]([C:6](=[O:7])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 66774Methyl GlycolateHCID 218782716-Bromo-N-(4-Fluorophenyl)NicotinamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 10402760[5-(4-Fluorophenylcarbamoyl)Pyridin-2-Yloxy]Acetic Acid Methyl EsterYield 65.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 6-bromo-N-(4-fluorophenyl)nicotinamide (1.0 g, 3.4 mmol), methyl glycolate (1.6 mL, 19 mmol), and potassium tert-butoxide (1.5 g, 13.6 mmol) in THF (10 mL) was heated in a sealed tube at 70° C. After 3 h the reaction mixture was poured onto ice and the solids isolated by filtration. Purification on silica gel by column chromatography using 30% ethyl acetate in hexanes gave 0.68 g (65%) of the titled product as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 10.30 (s 1H), 8.66 (m, 1H), 8.22 (m, 1H), 7.73 (m, 2H), 7.16 (m, 2H), 7.04 (m, 1H), 4.98 (s, 2H), 3.65 (s, 3H); MS (EI) m/z 303.13 (M−H)−.

Workup

  1. additionAfter 3 h the reaction mixture was poured onto ice
  2. customthe solids isolated by filtration
  3. customPurification on silica gel by column chromatography

Sources & evidence

ORD record
ord-b91ea66b2e9f4ea8b3ce2c3a4e6b456b
Source dataset
uspto-grants-2006_12
Patent number
US07151112B1

Reaction notes

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