Tetrahydrofuran → 2,2-Dimethyl-3-[2-methylthio-2-methoxycarbonyl-ethenyl]-cyclopropane-carboxylic acid

HRID 637324Notes

Reaction equation

HRID 637324 reaction equation
[CH3:1][C:2]1([CH3:10])[C@@H:7]2[C@H:3]1[C:4](=O)[O:5][C@H:6]2[OH:8].CC[C:13](OC)=[S:14].P(O)(O)([O-])=[O:18].[Na+].[O:23]1[CH2:27]C[CH2:25][CH2:24]1>>[CH3:10][C:2]1([CH3:1])[CH:3]([CH:4]=[C:25]([S:14][CH3:13])[C:24]([O:23][CH3:27])=[O:18])[CH:7]1[C:6]([OH:8])=[O:5]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10931532(1R, 4R, 5S) 4-Hydroxy-6,6-dimethyl-3-oxabicyclo(3.1.0)hexan-2-oneHCID 12787000O-Methyl propanethioateHCID 23672064Monosodium phosphate

Product 1

HCID 538922342,2-Dimethyl-3-[2-methylthio-2-methoxycarbonyl-ethenyl]-cyclopropane-carboxylic acidYield 10%

Conditions

Temperature
-60 °C

Procedure

A solution of 8.97 g of potassium tert.-butylate in 50 ml of tetrahydrofuran was slowly added at -60° C. to a solution of 5.6 of (1R,5S) 6,6-dimethyl-4(R)-hydroxy-3-oxa-bicyclo[3,0,1]hexane-2-one, 5.28 g of methyl methylthioacetate and 75 ml of tetrahydrofuran and the mixture was stirred at -60° C. for one hour and was admixed with saturated aqueous monosodium phosphate. The mixture was extracted with ethyl acetate and the organic phase was evaported to dryness under reduced pressure. The residue was taken up in benzene and 100 mg of p-toluene sulfonic acid were added thereto. The mixture was refluxed for 90 minutes and water was removed by azeotropic distillation. 12 ml of triethylamine were added to the mixture which was then refluxed for 3 hours and evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with a 1-1 cyclohexane-ethyl acetate mixture to obtain 6.3 g of (1R,cis,ΔZ) 2,2-dimethyl-3-[2-methylthio-2-methoxycarbonyl-ethenyl]-cyclopropane-carboxylic acid containing 10% of ΔE isomer according to its NMR spectrum.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. addition100 mg of p-toluene sulfonic acid were added
  3. temperatureThe mixture was refluxed for 90 minutes
  4. customwater was removed by azeotropic distillation
  5. addition12 ml of triethylamine were added to the mixture which
  6. temperaturewas then refluxed for 3 hours
  7. customevaporated to dryness under reduced pressure
  8. customThe residue was chromatographed over silica gel
  9. washwas eluted with a 1-1 cyclohexane-ethyl acetate mixture

Sources & evidence

ORD record
ord-1884806ad6f24bc2958bfabd68f4c4bc
Source dataset
uspto-grants-1985_12
Patent number
US04556666

Reaction notes

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