Glycine → (3Ar,7as)-hexahydro-2-benzofuran-1(3h)-one

HRID 1416859Notes

Reaction equation

HRID 1416859 reaction equation
NCC(O)=O.[OH-].[Na+].[C@@H:8]1([CH2:16][OH:17])[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][OH:15].COC1C=CC(C=O)=CC=1>O.CC(C)=O.C(O)C.C1C=[N+]([C@@H]2O[C@H](COP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](O)[C@@H]3O)(O)=O)([O-])=O)[C@@H](O)[C@H]2O)C=C(C(N)=O)C=1.C(OCC)(=O)C.C(Cl)Cl>[C@H:9]12[CH2:14][O:15][C:16](=[O:17])[C@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10]2

Participants

10

Reactant 4

HCID 750Glycine2×HCID 14798Sodium Hydroxide4×HCID 312444-MethoxybenzaldehydeHCID 2724019cis-1,2-Cyclohexanedimethanol

Product 1

HCID 245563(3Ar,7as)-hexahydro-2-benzofuran-1(3h)-oneYield 87.4%

Reagents, catalysts & solvents 5

HCID 5892NadideCatalystHCID 180AcetoneSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cyclohexane dimethanol (10.0 grams) is dissolved in 150 ml of acetone added to the glycine solution with stirring, followed by the addition of β-NAD+ (Sigma, 0.5 grams). To the resulting solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,6S)-(+)-8-oxabicyclo[4.3.0]nonan-7-one (8.5 grams) as a yellowish oil.

Workup

  1. dissolutionAfter the enzyme has dissolved the pH
  2. stirringthe reaction mixture is stirred at 30° C
  3. customDuring the reaction
  4. temperatureheating)
  5. extractionextracted 3 times with 250 ml of methylene chloride
  6. extractionfollowed by continuous extraction with 1 liter of ethyl acetate for 24 hours
  7. extractionThe ethyl acetate extract
  8. dry with materialis dried over anhydrous magnesium sulfate
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-0ca77f30c1c8421f8ba75e113fbe8bc4
Source dataset
uspto-grants-1999_06
Patent number
US05916786

Reaction notes

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