P-Cresol → (S)-2-hydroxy-3-(4-methoxyphenoxy)-N-(4-methoxyphenyl)-2-methylpropanamide

HRID 476340Notes

Reaction equation

HRID 476340 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][CH:4]=1.C[C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1.[C:24]([O-:27])([O-])=O.[K+].[K+]>C(O)(C)C>[OH:13][C@@:12]([CH3:15])([CH2:14][O:23][C:20]1[CH:19]=[CH:18][C:17]([O:27][CH3:24])=[CH:22][CH:21]=1)[C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:11]

Participants

5

Reactant 3

HCID 2879P-CresolHCID 11430Potassium CarbonateHCID 86616421(S)-N-(4-methoxyphenyl)-2-methyloxirane-2-carboxamide

Product 1

HCID 57608121(S)-2-hydroxy-3-(4-methoxyphenoxy)-N-(4-methoxyphenyl)-2-methylpropanamideYield 98.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

(S)—N-(4-Methoxyphenyl)-2-methyloxirane-2-carboxamide (0.50 g, 2.41 mmol), 4-methylphenol (0.39 g, 3.14 mmol) and K2CO3 (0.67 g, 4.82 mmol) were placed in a 250 mL round-bottomed flask fitted with a stirring bar. 100 mL of isopropanol was added at room temperature. The reaction solution was heated to reflux for 3 hours. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography (silica gel, EtOAc/hexanes=2/3 v/v) to give a white solid product, (S)-2-hydroxy-3-(4-methoxyphenoxy)-N-(4-methoxyphenyl)-2-methylpropanamide (6d), 0.79 g, 98.8% yield.

Workup

  1. customfitted with a stirring bar
  2. temperatureThe reaction solution was heated
  3. temperatureto reflux for 3 hours
  4. customThe solvent was removed under reduced pressure
  5. customThe residue was purified by flash column chromatography (silica gel, EtOAc/hexanes=2/3 v/v)

Sources & evidence

ORD record
ord-87a3cc0570b44e8da2f462fbb2345361
Source dataset
uspto-grants-2014_01
Patent number
US08637706B2

Reaction notes

Loading…