1-[2-[[Tert-butyl(dimethyl)silyl]oxymethyl]-6-(methoxymethoxy)-3-methyl-phenyl]cyclobutanol → 7-methylspiro[1H-isobenzofuran-3,1'-cyclobutane]-4-ol

HRID 527637Notes

Reaction equation

HRID 527637 reaction equation
[Si](O[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]([O:17]COC)[C:11]=1[C:21]1([OH:25])[CH2:24][CH2:23][CH2:22]1)(C(C)(C)C)(C)C>C(OCC)(=O)C.S(=O)(=O)(O)O>[CH3:16][C:15]1[C:10]2[CH2:9][O:25][C:21]3([CH2:22][CH2:23][CH2:24]3)[C:11]=2[C:12]([OH:17])=[CH:13][CH:14]=1

Participants

4

Reactant 1

HCID 679582151-[2-[[Tert-butyl(dimethyl)silyl]oxymethyl]-6-(methoxymethoxy)-3-methyl-phenyl]cyclobutanol2×

Product 1

HCID 866984537-methylspiro[1H-isobenzofuran-3,1'-cyclobutane]-4-olYield 77.1%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 1-[2-[[tert-butyl(dimethyl)silyl]oxymethyl]-6-(methoxymethoxy)-3-methyl-phenyl]cyclobutanol (Intermediate 175, 0.05 g, 0.136 mmoli) in Ethyl Acetate (5 ml), Sulphuric Acid (96%, 2 drops) was added at room temperature and the reaction mixture was stirred for 2 h. Ethyl Acetate (20 ml) was added and the organic phase was washed with brine (2×50 ml), dried over sodium sulphate and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluents affording the title compound (0.02 g) as a colourless oil.

Workup

  1. washthe organic phase was washed with brine (2×50 ml)
  2. dry with materialdried over sodium sulphate
  3. customevaporated
  4. customThe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluents

Sources & evidence

ORD record
ord-fd3a7bea445f4598a07f2a576e86859b
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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