Diisopropylethylamine → allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 1464731Notes

Reaction equation

HRID 1464731 reaction equation
[C:1]([Si:5]([CH3:28])([CH3:27])[O:6][C@@H:7]([C@H:9]1[C:15](=[O:16])[N:14]2[C@@H:10]1[C@@H:11]([CH3:26])[C:12]([S:23]([CH3:25])=O)=[C:13]2[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH2:29]([O:32][C:33]([N:35]1[CH2:39][C@@H](S)[CH2:37][C@H:36]1[CH2:41][O:42][CH2:43][CH2:44][F:45])=[O:34])[CH:30]=[CH2:31].C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)C>[CH2:29]([O:32][C:33]([N:35]1[CH2:39][C@@H:25]([S:23][C:12]2[C@H:11]([CH3:26])[C@H:10]3[N:14]([C:15](=[O:16])[C@@H:9]3[C@H:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:28])[CH3:27])[CH3:8])[C:13]=2[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[CH2:37][C@H:36]1[CH2:41][O:42][CH2:43][CH2:44][F:45])=[O:34])[CH:30]=[CH2:31]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57241269(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethoxymethyl)-4-mercaptopyrrolidineHCID 86747784allyl (4R,5S,6S)-6-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-methyl-3-methylsulfinyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

Product 1

HCID 57089568allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl]thio-6-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 43.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of allyl (4R,5S,6S)-6-[(1R)-1-(tertbutyldimethylsilyloxy)ethyl]-4-methyl-3-methylsulfinyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (33 mg) and (2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)-4-mercaptopyrrolidine (21 mg) in N,N-dimethylformamide (1.0 ml) was added diisopropylethylamine (10 mg). After stirring for 2 hours at ambient temperature, the solution was diluted with diethyl ether (10 ml) and washed with water, 1N hydrochloric acid, aqueous sodium bicarbonate solution and brine, dried, and evaporated under reduced pressure. The residue was purified by preparative thin layer chromatography [ethyl acetate-n-hexane (1:1.5, V/V)] to give allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-ylthio]-6-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (21 mg).

Workup

  1. washwashed with water, 1N hydrochloric acid, aqueous sodium bicarbonate solution and brine
  2. customdried
  3. customevaporated under reduced pressure
  4. customThe residue was purified by preparative thin layer chromatography [ethyl acetate-n-hexane (1:1.5, V/V)]

Sources & evidence

ORD record
ord-527a11e1bcbc41588fcf0a300e563824
Source dataset
uspto-grants-1994_04
Patent number
US05306816

Reaction notes

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