Hydrochloric Acid → HCID 57236660, compound

HRID 1975479Notes

Reaction equation

HRID 1975479 reaction equation
[CH2:1]([O:4][C:5]([N:7]([CH2:9][C@H:10]([CH2:14][NH:15][C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[C:11](=[O:13])[CH3:12])[CH3:8])=[O:6])[CH:2]=[CH2:3].C(N1CCCCC1)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(O[C@H:46]1[NH:49][C:48](=[O:50])[C@@H:47]1[C@H:51]([O:53][Si:54]([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55])[CH3:52])(=O)C.Cl>ClCCl.O.C(OCC)(=O)C.[Br-].[Zn+2].[Br-]>[CH2:1]([O:4][C:5]([N:7]([CH2:9][C@H:10]([CH2:14][NH:15][C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[C:11](=[O:13])[CH2:12][C@H:46]1[NH:49][C:48](=[O:50])[C@@H:47]1[C@H:51]([O:53][Si:54]([C:57]([CH3:58])([CH3:60])[CH3:59])([CH3:56])[CH3:55])[CH3:52])[CH3:8])=[O:6])[CH:2]=[CH2:3]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 13007N-Ethylpiperidine2×HCID 65367Trimethylsilyl triflate2×HCID 10935078AzetidonHCID 53768996HCID 53768996, compound

Product 1

HCID 57236660HCID 57236660, compoundYield 75.5%

Reagents, catalysts & solvents 4

HCID 10421208Zinc bromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S)-1-(N-allyloxycarbonyl-N-methylamino)-2-(allyloxycarbonylaminomethyl)butan-3-one (14.59 g) in dichloromethane (110 ml) were added N-ethylpiperidine (13.5 ml) and trimethylsilyl trifluoromethanesulfonate (18.9 ml) at -10° C. and the resulting mixture was stirred at ambient temperature for 1 hour. To a solution of (3R,4R)-4-acetoxy-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone (21.1 g) in dichloromethane (140 ml) were added N-ethylpiperidine (10.1 ml) and trimethylsilyl trifluoromethanesulfonate (14.2 ml) at -20° C. and the mixture was stirred at 0° C. for 1 hour. To a mixture of the latter solution and zinc bromide (44.05 g) was added the former solution at 0° C. and the resulting mixture was allowed to stir at ambient temperature for 2 hours. The reaction mixture was diluted with a mixture of water (800 ml) and ethyl acetate (800 ml). After adjusting pH to 0.7 with hydrochloric acid (6N), the mixture was allowed to stir at ambient temperature for 2 hours. The separated organic layer was washed in turn with water and brine. After adjusting pH to 7 with aqueous sodium hydrogen carbonate, the organic layer was washed with brine, dried over magnesium sulfate. Evaporation of the solvent gave a residue which was chromatographed on silica gel (1.5 l) eluting with a mixture of n-hexane and ethyl acetate (9:1-2:8, V/V) to give (3S,4R)-4-[(3S)-4-(N-allyloxycarbonyl-N-methylamino)-3-(allyloxycarbonylaminomethyl)-2-oxobutyl]-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidine (19.42 g).

Workup

  1. stirringthe mixture was stirred at 0° C. for 1 hour
  2. additionwas added the former solution at 0° C.
  3. stirringto stir at ambient temperature for 2 hours
  4. stirringto stir at ambient temperature for 2 hours
  5. washThe separated organic layer was washed in turn with water and brine
  6. washthe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customEvaporation of the solvent
  9. customgave a residue which
  10. customwas chromatographed on silica gel (1.5 l)
  11. washeluting with a mixture of n-hexane and ethyl acetate (9:1-2:8, V/V)

Sources & evidence

ORD record
ord-4e6594da3af44696bbc232fa15541312
Source dataset
uspto-grants-1994_02
Patent number
US05286721

Reaction notes

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