Hexane → (3S,4S,1R)-4-tert-butoxycarbonyl-1-tert-butoxycarbonylmethyl-3-(1'-hydroxyethyl)-azetidin-2-one

HRID 1034463Notes

Reaction equation

HRID 1034463 reaction equation
[C:1]([O:5][C:6]([CH2:8][N:9]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:15])[C@@H:11]1[O:14][C@@H:12]1[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].CCCCCC.C(OCC)(=O)C>O1CCCC1.C(Cl)Cl>[C:1]([O:5][C:6]([C@H:8]1[N:9]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10](=[O:15])[C@@H:11]1[C@H:12]([OH:14])[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8058HexaneHCID 8857Ethyl AcetateHCID 2733832Lithium HexamethyldisilazideHCID 54040080(2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide

Product 1

HCID 22851848(3S,4S,1R)-4-tert-butoxycarbonyl-1-tert-butoxycarbonylmethyl-3-(1'-hydroxyethyl)-azetidin-2-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 13.18 g of (2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide in 100 ml of tetrahydrofuran is cooled with stirring to -15°, and 100 ml of a 0.5-molar solution of lithium hexamethyldisilazide in tetrahydrofiran is added at temperatures between -15° and -10°. The progress of the reaction is followed by thin layer chromatography (solvent: a 1:1 mixture of hexane and ethyl acetate); the reaction is complete after stirring for about 4 hours at the temperature indicated above. The reaction mixture is diluted with methylene chloride and poured onto ice, and the organic layer is washed successively with water, twice with 0.1N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and water. The wash water is extracted twice with methylene chloride, and the combined organic phases are dried over sodium sulfate and evaporated under a water pump vacuum. After flash chromatography over 750 g of silica gel 60 (0.040-0.063 mm, Merck; elution with a 6:4 mixture of hexane and ethyl acetate), the crude product obtained gives (3S,4S,1R)-4-tert-butoxycarbonyl-1-tert-butoxycarbonylmethyl-3-(1'-hydroxyethyl)-azetidin-2-one, which melts at 79°-81°; [α]D -22.6° (c=0.574% in chloroform).

Workup

  1. stirringafter stirring for about 4 hours at the temperature
  2. additionpoured onto ice
  3. washthe organic layer is washed successively with water, twice with 0.1N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and water
  4. extractionThe wash water is extracted twice with methylene chloride
  5. dry with materialthe combined organic phases are dried over sodium sulfate
  6. customevaporated under a water pump vacuum
  7. washelution
  8. additionwith a 6:4 mixture of hexane and ethyl acetate), the crude product
  9. customobtained

Sources & evidence

ORD record
ord-c2fa559f05304e59bde47e2be8ba54ea
Source dataset
uspto-grants-1994_05
Patent number
US05317100

Reaction notes

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