Sodium hydride → 1-(tert-butyldimethylsilyloxy)-2-[3-(4,5-dihydro-4(R)-phenyloxazol-2-yl)phenoxy]ethane

HRID 2395378Notes

Reaction equation

HRID 2395378 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][CH2:10][C@@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:12]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C)C=O>[Si:25]([O:24][CH2:23][CH2:22][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[O:9][CH2:10][C@@H:11]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:12]=2)[CH:3]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 18665562(R)-3-(4-Phenyl-4,5-dihydrooxazol-2-yl)phenol

Product 1

HCID 186655451-(tert-butyldimethylsilyloxy)-2-[3-(4,5-dihydro-4(R)-phenyloxazol-2-yl)phenoxy]ethaneYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4,5-dihydro-2-(3-hydroxyphenyl)-4(R)-phenyloxazole (3.3 g, 13.8 mmol) in N,N-dimethylformamide (30 ml) was added sodium hydride (60% in mineral oil, 0.62 g, 16 mmol) portionwise over 5 min. at ambient temperature. The mixture was stirred for 1 hour, and then a solution of 2-bromo-1-(tert-butyldimethylsilyloxy)ethane (4.94 g, 21 mmol) in N,N-dimethylformamide (5 ml) was added dropwise over 5 min. and the reaction mixture stayed overnight. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml), the aqueous layer was separated, extracted with ethyl acetate (2×50 ml) and the combined organic phase washed with 1N HCl (100 ml), aqueous 4% NaHCO3 solution (100 ml) and brine (100 ml), dried (MgSO4) and evaporated. The resulting residue was purified by column chromatography on silica gel eluting with ethyl acetate/n-hexane (=1:6) to afford 1-(tert-butyldimethylsilyloxy)-2-[3-(4,5-dihydro-4(R)-phenyloxazol-2-yl)phenoxy]ethane (4.7 g, 86%) as a colorless oil.

Workup

  1. waitthe reaction mixture stayed overnight
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml)
  3. customthe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×50 ml)
  5. washthe combined organic phase washed with 1N HCl (100 ml), aqueous 4% NaHCO3 solution (100 ml) and brine (100 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe resulting residue was purified by column chromatography on silica gel eluting with ethyl acetate/n-hexane (=1:6)

Sources & evidence

ORD record
ord-50501b7d35f94f229783c4580faf4120
Source dataset
uspto-grants-1998_09
Patent number
US05814648

Reaction notes

Loading…