Water → (S)-2-hydroxy-3-(4-hydroxyphenoxy)-N-(4-hydroxyphenyl)-2-methylpropanamide

HRID 1694776Notes

Reaction equation

HRID 1694776 reaction equation
[OH:1][C@@:2]([CH3:24])([CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][CH:17]=1)[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([O:12]C)=[CH:8][CH:7]=1)=[O:4].B(Br)(Br)Br.O.CCOC(C)=O>C(Cl)Cl>[OH:1][C@@:2]([CH3:24])([CH2:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=1)[C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([OH:12])=[CH:10][CH:11]=1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 57608121(S)-2-hydroxy-3-(4-methoxyphenoxy)-N-(4-methoxyphenyl)-2-methylpropanamide

Product 1

HCID 57608118(S)-2-hydroxy-3-(4-hydroxyphenoxy)-N-(4-hydroxyphenyl)-2-methylpropanamideYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-hydroxy-3-(4-methoxyphenoxy)-N-(4-methoxyphenyl)-2-methylpropanamide (6d) (0.20 g, 0.60 mmol) was dissolved in dry CH2Cl2 (30 mL). BBr3 (4 mL of 1.0 M CH2Cl2 solution) was added dropwise with stirring via a syringe at room temperature. The reaction solution was allowed to stir overnight at room temperature. The mixture was cooled to 0° C. in a ice bath and hydrolyzed by adding water (25 mL). EtOAc (50 mL) was added to partition the solution. The organic layer was separated; the aqueous layer was extracted with EtOAc (2×10 mL). The organic layers were combined, washed with brine and dried over anhydrous MgSO4. The solvent was removed under vacuum. The residue was purified by flash column chromatography using silica-gel with hexanes/EtOAc (3/7 v/v) to afford a white solid product, (S)-2-hydroxy-3-(4-hydroxyphenoxy)-N-(4-hydroxyphenyl)-2-methylpropanamide (6f), 0.13 g, 67.2% yield.

Workup

  1. stirringto stir overnight at room temperature
  2. temperatureThe mixture was cooled to 0° C. in a ice bath
  3. customto partition the solution
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  6. washwashed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. customThe solvent was removed under vacuum
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-dec114819ff14faa80dd45a95789ab4e
Source dataset
uspto-grants-2012_04
Patent number
US08158828B2

Reaction notes

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