3-Oxotetrahydrofuran → 3-(7-Methoxybenzofuran-2-yl)-tetrahydrofuran-3-ol

HRID 1282031Notes

Reaction equation

HRID 1282031 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[C:16]2[O:15][CH:14]=[CH:13][C:12]=2[CH:11]=[CH:10][CH:9]=1.[O:17]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18]1>O1CCCC1>[CH3:6][O:7][C:8]1[C:16]2[O:15][C:14]([C:19]3([OH:22])[CH2:20][CH2:21][O:17][CH2:18]3)=[CH:13][C:12]=2[CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 5293923-OxotetrahydrofuranHCID 5904627-MethoxybenzofuranHCID 178418339Butyllithium

Product 1

HCID 184236483-(7-Methoxybenzofuran-2-yl)-tetrahydrofuran-3-olYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Methyl sulfoxide (1.16 ml) was added dropwise to a stirred solution of oxalyl chloride (0.71 ml) in dry dichloromethane (15 ml) at −60° C. under an inert atmosphere. After stirring at this temperature for 30 minutes a solution of 3-hydroxytetrahydrofuran (0.55 ml) in dry dichloromethane was added carefully. After a further 30 minutes triethylamine was added dropwise and the reaction allowed to warm to room temperature. The reaction was poured onto water (40 ml) and extracted with dichloromethane (30 ml). The organic phase was washed with water (50 ml), brine (2×50 ml) and saturated aqueous sodium hydrogen carbonate solution (2×50 ml). After drying over magnesium sulphate the solvent was removed in vacuo to afford tetrahydro-furan-3 -one as a yellow gum (0.19 g). n-Butyllithium (0.72 ml, 1.6M in hexanes) was added dropwise to a stirred solution of 7-methoxybenzofuran (0.15 g) in dry tetrahydrofuran (5 ml) at −78° C. under a dry nitrogen atmosphere. After stirring for 20 minutes a solution of tetrahydrofuran-3 -one (90 mg) in dry tetrahydrofuran (2 ml) was added carefully. After stirring for a further 15 minutes at −78° C. the reaction was allowed to warm to room temperature. The reaction was carefully quenched with water and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (2×15 ml) and water (15 ml). The combined organic extracts were dried over magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica eluting with 50% ethyl acetate in hexane to give the title compound as an orange gum (64 mg).

Workup

  1. additionwas added carefully
  2. temperatureto warm to room temperature
  3. customThe reaction was carefully quenched with water
  4. customthe solvent removed in vacuo
  5. customThe residue was partitioned between ethyl acetate (2×15 ml) and water (15 ml)
  6. dry with materialThe combined organic extracts were dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on silica eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-673910932f4f420fb4077e08ef35b2fd
Source dataset
uspto-grants-2002_09
Patent number
US06455561B1

Reaction notes

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