N-Ethylpiperidine → HCID 57233973, compound

HRID 1090528Notes

Reaction equation

HRID 1090528 reaction equation
C(O[C@H:5]1[NH:8][C:7](=[O:9])[C@@H:6]1[C@H:10]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH3:11])(=O)C.C(N1CCCCC1)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[CH2:40]([O:43][C:44]([N:46]1[CH2:50][C@H:49]([O:51][CH3:52])[CH2:48][C@H:47]1[CH:53]=[C:54]([CH3:58])[C:55](=[O:57])[CH3:56])=[O:45])[CH:41]=[CH2:42].C(=O)([O-])O.[Na+]>ClCCl.O.C(OCC)(=O)C>[CH2:40]([O:43][C:44]([N:46]1[CH2:50][C@H:49]([O:51][CH3:52])[CH2:48][C@H:47]1[CH:53]=[C:54]([CH3:58])[C:55](=[O:57])[CH2:56][C@H:5]1[NH:8][C:7](=[O:9])[C@@H:6]1[C@H:10]([O:12][Si:13]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15])[CH3:11])=[O:45])[CH:41]=[CH2:42]

Participants

9

Reactant 5

HCID 13007N-Ethylpiperidine2×HCID 65367Trimethylsilyl triflate2×HCID 516892Sodium BicarbonateHCID 10935078AzetidonHCID 57315470HCID 57315470, compound

Product 1

HCID 57233973HCID 57233973, compoundYield 64.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3R,4R)-4-acetoxy-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidine (2.90 g) and N-ethylpiperidine (1.35 ml) in dichloromethane (15 ml) and added trimethylsilyl trifluoromethanesulfonate (1.95 ml) at -20° C., and the resulting mixture was stirred at 0° C. for 1 hour (Solution A). To a solution of (2S,4R)-1-allyloxycarbonyl-4-methoxy-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine (2.70 g) and N-ethylpiperidine (1.48 ml) in dichloromethane (50 ml) was added trimethylsilyl trifluoromethanesulfonate (2.93 ml) at -20° C. and the resulting mixture was stirred at 0° C. for 1 hour. To this mixture was added dropwise the above obtained Solution A at 0° C. and the resulting mixture was stirred for another 1 hour at 0° C. The reaction mixture was taken up into a mixture of ethyl acetate (300 ml) and water (300 ml) and the mixture was stirred at ambient temperature for 2 hours. After adjusting pH to around 6.5 with aqueous sodium hydrogen carbonate, the organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (120 ml) eluting with a mixture of n-hexane and ethyl acetate (1:1 V/V) to give (3S,4R)-4-[4-{(2S,4R)-1-allyloxycarbonyl-4-methoxypyrrolidin-2-yl}-3-methyl-2-oxo-3-butenyl]-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidine (3.24 g).

Workup

  1. stirringthe resulting mixture was stirred for another 1 hour at 0° C
  2. stirringthe mixture was stirred at ambient temperature for 2 hours
  3. customthe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was chromatographed on silica gel (120 ml)
  8. washeluting with a mixture of n-hexane and ethyl acetate (1:1 V/V)

Sources & evidence

ORD record
ord-e63179fb8b304711943f9e036d7bc394
Source dataset
uspto-grants-1992_01
Patent number
US05081237

Reaction notes

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