Tetrahydrofuran → 2-[5-(4-{1-[4-(t-Butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-yl]-propan-2-ol

HRID 546836Notes

Reaction equation

HRID 546836 reaction equation
[CH3:1][Mg]Br.COC(C1OC([C:13]2[CH:18]=[CH:17][C:16]([C:19]([C:24]3[CH:29]=[CH:28][C:27]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[C:26]([CH3:38])[CH:25]=3)([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:15][C:14]=2[CH3:39])=CC=1)=O.C([O:43][CH2:44][CH3:45])(=O)C.[O:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1>>[C:34]([Si:31]([CH3:32])([CH3:33])[O:30][C:27]1[CH:28]=[CH:29][C:24]([C:19]([C:16]2[CH:17]=[CH:18][C:13]([C:50]3[O:46][C:47]([C:44]([OH:43])([CH3:45])[CH3:1])=[CH:48][CH:49]=3)=[C:14]([CH3:39])[CH:15]=2)([CH2:20][CH3:21])[CH2:22][CH3:23])=[CH:25][C:26]=1[CH3:38])([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8857Ethyl AcetateHCID 57709087HCID 57709087, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 670651812-[5-(4-{1-[4-(t-Butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-yl]-propan-2-ol

Procedure

A 3 M solution of methylmagnesium bromide in tetrahydrofuran (0.08 mL, 0.24 mmol) was added to a solution of 5-(4-{1-[4-(t-butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-carboxylic acid methyl ester (Example 19-(2); 20 mg, 0.039 mmol) in tetrahydrofuran (0.2 mL) at 0° C., and the mixture was stirred at the same temperature for three hours. Ethyl acetate was added to the reaction solution. The organic layer was washed with a sodium bisulfate aqueous solution and brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give crude 2-[5-(4-{1-[4-(t-butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-yl]-propan-2-ol (8.5 mg). A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.03 mL, 0.03 mmol) was added to a solution of the resulting compound in tetrahydrofuran (0.2 mL), and the mixture was stirred at room temperature for one minute. Ethyl acetate was added to the reaction mixture. The organic layer was washed with distilled water and brine and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. (R)-(−)-Dihydro-5-(p-tolyl-sulfonyloxymethyl)-2(3H)-furanone (11 mg, 0.041 mmol) and potassium carbonate (9 mg, 0.066 mmol) were added to a solution of the residue (6.5 mg) in N,N-dimethylformamide (0.2 mL) at room temperature, and the mixture was stirred at room temperature for 11 hours. Ethyl acetate was added to the reaction solution. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=1/1) to give the title compound (2.8 mg, 34.5%).

Workup

  1. washThe organic layer was washed with a sodium bisulfate aqueous solution and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. distillationThen, the solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-72b911fe10b744488363c52ca9b8cc43
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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