Water → N-[3-(2-Hydroxyethyl)-4-methoxy-[1,1'-biphenyl]-2-yl]-2,2-dimethylpropanamide

HRID 617408Notes

Reaction equation

HRID 617408 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:5]([NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])[CH:4]=1.C([Li])CCC.[CH2:27]1[O:29][CH2:28]1.O>C1COCC1.C(O)(=O)C>[OH:29][CH2:28][CH2:27][C:4]1[C:5]([NH:15][C:16](=[O:21])[C:17]([CH3:18])([CH3:20])[CH3:19])=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]

Participants

7

Reactant 4

HCID 962WaterHCID 6354Ethylene OxideHCID 21852181N-(4-methoxybiphenyl-2-yl)-2,2-dimethylpropionamideHCID 178418339Butyllithium

Product 1

HCID 21852186N-[3-(2-Hydroxyethyl)-4-methoxy-[1,1'-biphenyl]-2-yl]-2,2-dimethylpropanamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

A mechanically stirred solution of N-(4-methoxybiphenyl-2-yl)-2,2-dimethylpropionamide (17.91 g, 63.2 mmol) in anhydrous THF at -68° C. was treated dropwise with butyllithium (2.46 M in hexane, 72.0 mL, 177 mmol), stirred 1 h, allowed to warm to -5° C., stirred 1 h, cooled to -78° C., and treated with ethylene oxide (10.0 mL, 8.82 g, 200 mmol) in one portion. The suspension was allowed to warm to room temperature and stirred for 12 h. The suspension was treated with water (50 mL) and glacial acetic acid (2 mL), stirred 10 min, and concentrated in vacuo. The residue was treated with water (500 mL) and Et2O (300 mL), and the layers were separated. The aqueous layer was further extracted with diethyl ether (2×300 mL), the combined organic extracts were washed with saturated sodium bicarbonate (500 mL), brine (500 mL), dried (K2CO3), filtered, and concentrated in vacuo to give a solid. Recrystallization from Et2O/hexanes gave 10.85 g (52%, 2 crops) of the compound as white crystals: 1H NMR (300 MHz, CDCl3) δ 1.04 (s, 9H), 2.00 (br s, 1H), 2.89 (t, J=6 Hz, 2H), 3.85 (s, 3H), 3.91 (t, J=6 Hz, 2H), 6.88 (d, J=8 Hz, 1H), 7.18 (d, J=8 Hz, 1H), 7.26-7.36 (m, 5H), 7.50 (br s, 1H).

Workup

  1. stirringstirred 1 h
  2. temperaturecooled to -78° C.
  3. temperatureto warm to room temperature
  4. stirringstirred for 12 h
  5. stirringstirred 10 min
  6. concentrationconcentrated in vacuo
  7. additionThe residue was treated with water (500 mL) and Et2O (300 mL)
  8. customthe layers were separated
  9. extractionThe aqueous layer was further extracted with diethyl ether (2×300 mL)
  10. washthe combined organic extracts were washed with saturated sodium bicarbonate (500 mL), brine (500 mL)
  11. dry with materialdried (K2CO3)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a solid
  15. customRecrystallization from Et2O/hexanes

Sources & evidence

ORD record
ord-568f238fcc3d45e0a3f6d532f06bb400
Source dataset
uspto-grants-1999_09
Patent number
US05948817

Reaction notes

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