Hydroquinone → 4-{[tert-Butyl(diphenyl)silyl]oxy}phenol

HRID 618773Notes

Reaction equation

HRID 618773 reaction equation
[C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].N1C=CN=C1.[C:14]([Si:18]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)Cl)([CH3:17])([CH3:16])[CH3:15]>N1C=CC=CC=1>[Si:18]([O:2][C:1]1[CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 785HydroquinoneHCID 795ImidazoleHCID 94078tert-Butyldiphenylchlorosilane

Product 1

HCID 138044024-{[tert-Butyl(diphenyl)silyl]oxy}phenolYield 55.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

To a solution of 8.26 g of hydroquinone and 6.3 g of imidazole in 80 mL of pyridine was added 20.6 g of t-butyldiphenylchlorosilane in 20 mL of pyridine. After 1.5 h the mixture was partitioned between water and ethyl acetate. The organic layer was washed twice with phosphate buffer (pH 2) and once each with phosphate buffer (pH 8) and brine before being filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (85:15)] afforded 14.4 g of 4-(t-butyldiphenylsilyloxy)phenol. The structure was confirmed by its NMR spectrum. To a solution of 46 mg of 1,1'-carbonyldiimidazole in 0.5 mL nitromethane was added 65 μL of methyl triflate followed by 100 mg of 4-(t-butyldiphenylsilyloxy)phenol in 1.4 mL of nitromethane. A total of 1.9 mL of this solution was added to a mixture of 100 mg of phorbol 12,13-bis[(2',4'-difluorophenyl)acetate] and approximately 10 mg of 4-dimethylaminopyridine in 500 μL of anhydrous tetrahydrofuran. After 4.5 h this mixture was partitioned between ethyl acetate and water. The organic layer was filtered through N/N/S, concentrated in vacuo and subjected to preparative liquid chromatography [silica; hexane/ethyl acetate (80:20)] to afford 142 mg of 20-O-[4'-(t-butyldiphenylsilyloxy)phenoxy]carbonylphorbol 12,13-bis[(2',4'-difluorophenyl)acetate]. A solution of this material in 1 mL tetrahydrofuran was treated with 160 μL of 1.0M tetrabutylammonium fluoride in tetrahydrofuran. After 14 min the mixture was partitioned between ethyl acetate and phosphate buffer (pH 8). The organic layer was filtered through N/N/S and concentrated in vacuo. After preparative liquid chromatography [silica, hexane/ethyl acetate (65:35)] 108 mg of 20-O-(4'-hydroxyphenoxy)carbonylphorbol 12,13-bis[(2',4'-difluorophenyl)acetate] was obtained. The structure was confirmed by NMR and mass spectral analysis.

Workup

  1. customAfter 1.5 h the mixture was partitioned between water and ethyl acetate
  2. washThe organic layer was washed twice with phosphate buffer (pH 2)
  3. filtrationonce each with phosphate buffer (pH 8) and brine before being filtered through N/N/S
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cd2093dbd997414089a80349b3fb9554
Source dataset
uspto-grants-1999_09
Patent number
US05955501

Reaction notes

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