Sulfuric Acid → HCID 66902478, compound

HRID 2242307Notes

Reaction equation

HRID 2242307 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]2[CH:3]1[C@H:4]2[C:8]([O:10][CH2:11][CH3:12])=[O:9].S(=O)(=O)(O)O.[C:18](OC(C)=C)(=[O:20])[CH3:19]>>[C:18]([O:1][C:2]1[CH:3]2[CH:5]([CH2:6][CH:7]=1)[C@@H:4]2[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:20])[CH3:19]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 7916Isopropenyl acetateHCID 66902515HCID 66902515, compound2×

Product 1

HCID 66902478HCID 66902478, compound

Procedure

A mixture of ethyl (6S)-2-oxobicyclo[3.1.0]hexane-6-carboxylate (380.1 g, 2.26 mol) and sulfuric acid (18 M, 6.3 mL, 0.11 mol) in isopropenyl acetate (2.26 L) is heated at reflux using a Dean-Stark apparatus for 2.5 hours, at which time GC analysis revealed a 9:1 mixture of the title compound versus ethyl (6S)-2-oxobicyclo[3.1.0]hexane-6-carboxylate. After the removal of 950 mL of solvent by distillation over 1 hour, GC shows that the product/starting material ratio is 17:1. Additional isopropenyl acetate (900 mL) and conc. H2SO4 (3.15 mL) are added, and the mixture is stirred at reflux for another 15 hours, at which time GC shows 27:1 product/starting material. After another 1.35 L of solvent is distilled off, the mixture is cooled to room temperature before it is diluted with MTBE (2 L), H2O (250 mL), and aqueous saturated NaHCO3 (600 mL). The layers are separated and the organic layer is washed with brine (400 mL). The combined aqueous layers are extracted with MTBE (400 mL), and the combined organic layers are dried (Na2SO4), filtered, and concentrated to a dark red/brown oil (540 g). The crude oil is split into two equal portions and filtered through a pad of flash SiO2 (713 g for each batch), eluting with 10:1/heptane:ethyl acetate. The product-containing fractions from both plugs are combined and concentrated to afford the title compound as a yellow oil (460 g, 97%; 90% corrected for solvent by NMR). Column chromatography on silica gel eluting with ethyl acetate/hexanes (1:5) provides an analytically pure sample of the title compound as a colorless oil.

Workup

  1. temperatureis heated
  2. temperatureat reflux
  3. customfor 2.5 hours

Sources & evidence

ORD record
ord-eab58e0cddc14fcb8f049ddec01dbdcb
Source dataset
uspto-grants-2010_03
Patent number
US07671082B2

Reaction notes

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