Tetrahydrofuran → Methyl 2,2-diethyl-2,3-dihydro-7-methoxybenzofuran-4-carboxylate

HRID 1954043Notes

Reaction equation

HRID 1954043 reaction equation
[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)[C:4]1C=CC=C[CH:5]=1.[NH2-].[Na+].C1COCC1.[CH3:29][O:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][C:32]=1[O:41][CH:42]([CH3:47])[C:43](=O)[CH2:44]C>C1(C)C=CC=CC=1>[CH2:4]([C:42]1([CH2:43][CH3:44])[CH2:47][C:33]2=[C:34]([C:35]([O:37][CH3:38])=[O:36])[CH:39]=[CH:40][C:31]([O:30][CH3:29])=[C:32]2[O:41]1)[CH3:5]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 16212304Sodium;azanide;methyl(triphenyl)phosphanium;bromideHCID 22734323Methyl 4-methoxy-3-(1-methyl-2-oxobutoxy)benzoate

Product 1

HCID 22734147Methyl 2,2-diethyl-2,3-dihydro-7-methoxybenzofuran-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

10 of methyltriphenylphosphonium bromide-sodium amide mixture (FLUKA 69500) are added to 100 ml of abs. THF at about 10° C. under protective gas (nitrogen), and the mixture is warmed to RT and stirred for about 30 min. A solution of 5.3 g of methyl 4-methoxy-3-(1-methyl-2-oxobutoxy)benzoate is then added dropwise. The mixture is stirred at RT for 1 h, then poured onto water and extracted 3 times with about 50 ml of ethyl acetate. The combined extracts are dried over sodium sulfate and concentrated, and the oily residue is dried in a high vacuum. The oil obtained (3.8 g) is stirred at 190-200° C. for 1 h, cooled and dissolved in 100 ml of toluene. The solution is treated with 5 g of Amberlyst 15 and vigorously stirred at 80° C. overnight. The Amberlyst is then filtered off, the solution is concentrated and the residue is chromatographed on a silica gel column using ethyl acetate/petroleum ether 4:6. The chromatographically pure fractions are combined and concentrated, and the residue is dried in a high vacuum. 1.5 g of the title compound are obtained as a pale yellow oil.

Workup

  1. stirringThe mixture is stirred at RT for 1 h
  2. additionpoured onto water
  3. extractionextracted 3 times with about 50 ml of ethyl acetate
  4. dry with materialThe combined extracts are dried over sodium sulfate
  5. concentrationconcentrated
  6. customthe oily residue is dried in a high vacuum
  7. customThe oil obtained (3.8 g)
  8. stirringis stirred at 190-200° C. for 1 h
  9. temperaturecooled
  10. additionThe solution is treated with 5 g of Amberlyst 15
  11. stirringvigorously stirred at 80° C. overnight
  12. filtrationThe Amberlyst is then filtered off
  13. concentrationthe solution is concentrated
  14. customthe residue is chromatographed on a silica gel column
  15. concentrationconcentrated
  16. customthe residue is dried in a high vacuum

Sources & evidence

ORD record
ord-52802e97f1d94d2fbab785c05815d88c
Source dataset
uspto-grants-2000_09
Patent number
US06121274

Reaction notes

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