Sodium hydride → 3-(Benzhydrylideneamino)-8-oxabicyclo[3.2.1]octane-3-carboxylic Acid Ethyl Ester

HRID 1872884Notes

Reaction equation

HRID 1872884 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:22])[CH2:7][N:8]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:4].S(C1C=CC(C)=CC=1)(O)(=O)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.O[CH2:46][C@H:47]1[CH2:51][CH2:50][C@@H:49]([CH2:52]O)[O:48]1>CN(C)C=O>[CH2:3]([O:5][C:6]([C:7]1([N:8]=[C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:52][CH:49]2[O:48][CH:47]([CH2:51][CH2:50]2)[CH2:46]1)=[O:22])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 86755706cis-2,5-Bis(hydroxymethyl)tetrahydrofuran ditosylate

Product 1

HCID 544280513-(Benzhydrylideneamino)-8-oxabicyclo[3.2.1]octane-3-carboxylic Acid Ethyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of sodium hydride (0.41 grams, 17.1 mmole) in N,N-dimethylformamide (50 mL) at 0° C. was added dropwise a solution of N-diphenylmethylene glycine ethyl ester (2.07 grams, 7.8 mmol) in N,N-dimethylformamide (50 mL). After stirring for 30 minutes at room temperature, a solution of cis-2,5-bis(hydroxymethyl)-tetrahydrofuran ditosylate (4.1 grams, 9.3 mmole) in N,N-dimethylformamide (50 mL) was added dropwise. The reaction mixture was gradually heated to 100° C. in an oil bath and stirred at this temperature overnight. The solvent was evaporated under vacuum and the reside was taken up in water and extracted twice with diethyl ether. The combined organic extracts were washed with brine, dried over magnesium sulfate and concentrated to a brown oil, from which the title compound (1.42 grams, 51%, a 3:1 mixture of exo/endo diastereomers) was isolated by chromatography on silica gel (20% ethyl acetate in hexane as eluant).

Workup

  1. temperatureThe reaction mixture was gradually heated to 100° C. in an oil bath
  2. stirringstirred at this temperature overnight
  3. customThe solvent was evaporated under vacuum
  4. extractionextracted twice with diethyl ether
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated to a brown oil, from which the title compound (1.42 grams, 51%
  8. additiona 3:1 mixture of exo/endo diastereomers)
  9. customwas isolated by chromatography on silica gel (20% ethyl acetate in hexane as eluant)

Sources & evidence

ORD record
ord-1d894ca1741447e2a132b658125549bc
Source dataset
uspto-grants-2000_08
Patent number
US06110964

Reaction notes

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