Sodium hydride → (1(S)-benzyloxycarbonylamino-2-cyclohexyl-ethyl)oxirane

HRID 478028Notes

Reaction equation

HRID 478028 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[CH2:9]([O:16][C:17]([NH:19][C@@H:20]([CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[CH:21]=[O:22])=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1COCC1>[CH2:9]([O:16][C:17]([NH:19][C@H:20]([CH:21]1[CH2:4][O:22]1)[CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 10869979N-benzyloxycarbonyl-3-cyclohexylalaninal

Product 1

HCID 14158022(1(S)-benzyloxycarbonylamino-2-cyclohexyl-ethyl)oxirane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

18.9 g of sodium hydride dispersion (55% in oil) are freed of oil in a dry reaction flask under argon by stirring three times in 50 ml of petroleum ether (b.p. 40°-60°) and subsequently decanting off the solvent each time. After drying under a high vacuum, a grey powder is obtained which is placed in 500 ml of THF; 55.6 g of trimethylsulphoxonium iodide are added thereto, the temperature increasing to approximately 40°. The grey suspension is boiled under reflux for 1 hour and then, within a period of 50 minutes at -70°, a solution of 108.6 g of 2(S)-benzyloxycarbonylamino-3-cyclohexylpropanal in 250 ml of THF is added. The yellow suspension is stirred at 0° for 2 hours. The yellowish turbid solution is poured onto 500 g of ice. The aqueous solution is extracted with 2.5 liters of ether, and the organic phase is washed with water and, after being dried over sodium sulphate, concentrated by evaporation. The oily residue is separated by means of flash chromatography (2.5 kg of silica gel 60, 40-63 μm, eluant C). The product-containing fractions are combined, concentrated by evaporation and dried under a high vacuum. The title compound (diastereoisomeric mixture, approximately 4:1) is obtained in the form of a slightly yellowish oil. Rf (K)=0.71; Rf (C)=0.16.

Workup

  1. customsubsequently decanting off the solvent each time
  2. customAfter drying under a high vacuum
  3. customa grey powder is obtained which
  4. temperaturethe temperature increasing to approximately 40°
  5. temperatureunder reflux for 1 hour
  6. extractionThe aqueous solution is extracted with 2.5 liters of ether
  7. washthe organic phase is washed with water
  8. dry with materialafter being dried over sodium sulphate
  9. concentrationconcentrated by evaporation
  10. customThe oily residue is separated by means of flash chromatography (2.5 kg of silica gel 60, 40-63 μm, eluant C)
  11. concentrationconcentrated by evaporation
  12. customdried under a high vacuum

Sources & evidence

ORD record
ord-7eb4fac20655433385227723ab8206a1
Source dataset
uspto-grants-1989_12
Patent number
US04889869

Reaction notes

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