Methanol → methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

HRID 2401080Notes

Reaction equation

HRID 2401080 reaction equation
[CH3:1][O:2][C:3]([C:5]1([CH2:11][CH:12]=C)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].CO.CC[O:18]C(C)=O>CC(O)C.O.C(Cl)Cl.O=[Os](=O)(=O)=O>[CH3:1][O:2][C:3]([C:5]1([CH2:11][CH:12]=[O:18])[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1)=[O:4]

Participants

8

Reactant 3

HCID 887Methanol2×HCID 8857Ethyl AcetateHCID 58928641tetrahydro-4-(2-propen-1-yl)-2H-Pyran-4-carboxylic acid methyl ester

Product 1

HCID 58468045methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-Allyl-tetrahydro-pyran-4-carboxylic acid methyl ester (11 g, 59.78 mmol) was dissolved in iPrOH (300 mL). To this was added a aqueous solution of NaIO4 (28 g, 130.4 mmol, 2.18 equiv.) in water (300 mL), followed by addition of OsO4 (50 mg, crystals, in one portion) at rt. The solution was stirred with a mechanical stirrer at rt (water bath). After 30 min, milky cloudy mixture was formed. Stirring was continued for 4 h. TLC (1% MeOH in DCM, and 5% MeOH in DCM) did not detect the starting material. The reaction mixture was monitored by 1H NMR by taking an aliquot in CDCl3 periodically until no alkene peak was detected in the sample. At which time the reaction was judged to be complete. The reaction mixture was poured into ice water (200 mL) and EtOAc (200 mL). The two layers were separated and the aqueous layer was extracted with EtOAc (5×50 mL). More water was added to dissolve the solid to result a clear solution. The combined extracts were washed with brine, and concentrated to dryness to obtain the title compound as a crude liquid product. The product was subject to a distillation under reduced pressure to remove isopropanol. The residual product was then purified on a 80 g silica gel column, eluted with MeOH in DCM: 0% 0-5 min; 5-10% 5-25 min. 10-12% 25-60 min. Note: the product is not UV active. Anisaldehyde visualization was used. The product fractions were collected and concentrated to yield a liquid 6.6 g (60% yield) of the title compound.

Workup

  1. custommilky cloudy mixture was formed
  2. waitwas continued for 4 h
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (5×50 mL)
  5. additionMore water was added
  6. dissolutionto dissolve the solid
  7. customto result a clear solution
  8. washThe combined extracts were washed with brine
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-86d3a7f3d46e4de29385c2e34e969f56
Source dataset
uspto-grants-2014_08
Patent number
US08796278B2

Reaction notes

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