Sulfuric Acid → 1-(Tetrahydro-2H-pyran-4-yl)ethanone

HRID 2088877Notes

Reaction equation

HRID 2088877 reaction equation
[C:1]([C:4]1(C(OC)=O)[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(O)(C)C.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>O>[O:7]1[CH2:8][CH2:9][CH:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 9964279methyl 4-acetyltetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 98773651-(Tetrahydro-2H-pyran-4-yl)ethanoneYield 46.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

Combine methyl 4-acetyltetrahydro-2H-pyran-4-carboxylate (23.06 g, 123.84 mmol) with isopropyl alcohol (124 mL) and water (124 mL). Add sulfuric acid (33.00 mL, 5.0 eq). Heat the reaction mixture to 100° C. over two nights. Cool and add the reaction mixture slowly to a mixture of sodium bicarbonate (136 g) in water (1 L). Extract with dichloromethane. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by silica gel chromatography, eluting with hexanes to 25% ethyl acetate in hexanes to 50% ethyl acetate in hexanes, to give the title compound (7.39 g, 34%). 1H NMR (400 MHz, DMSO-d6) δ 3.79 (m, 2H), 3.27 (m, 2H), 2.54 (m, 1H), 2.05 (s, 3H), 1.66 (m, 2H), 1.38 (m, 2H).

Workup

  1. temperatureCool
  2. additionadd the reaction mixture
  3. extractionExtract with dichloromethane
  4. dry with materialDry the organics over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by silica gel chromatography
  8. washeluting with hexanes to 25% ethyl acetate in hexanes to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-84c353928459463ab44bf50770f8720c
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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