2,6-Lutidine → (3S, 4R)-3-[(R)-1-t-Butyldimethylsilyloxyethyl]-4-[1-methyl-2p-nitrobenzyloxycarbonylaminoethylthio(thiocarbonyl)]thio-1-[1-(p-nitrobenzyloxycarbonyl)triphenylphosphoranylidenemethyl]azetidin-2-one

HRID 1075220Notes

Reaction equation

HRID 1075220 reaction equation
[Si:1]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([S:15][C:16]([S:18][CH:19]([CH3:35])[CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=2)=[O:23])=[S:17])[N:13]([CH:36](O)[C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=2)=[O:38])[C:12]1=[O:51])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C(C)=CC=CC=1C.S(Cl)(Cl)=O.[C:64]1([P:70]([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>O1CCCC1.C(OCC)(=O)C>[Si:1]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([S:15][C:16]([S:18][CH:19]([CH3:35])[CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=2)=[O:23])=[S:17])[N:13]([C:36](=[P:70]([C:71]2[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=2)([C:77]2[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=2)[C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=2)[C:37]([O:39][CH2:40][C:41]2[CH:42]=[CH:43][C:44]([N+:47]([O-:49])=[O:48])=[CH:45][CH:46]=2)=[O:38])[C:12]1=[O:51])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79372,6-Lutidine2×HCID 11776TriphenylphosphineHCID 24386Thionyl ChlorideHCID 13175764(3S, 4R)-3-[(R)-1-t-Butyldimethylsilyloxyethyl]-1-[1-hydroxy-1-(p-nitrobenzyloxycarbonyl)methyl]-4-[1-methyl-2-p-nitrobenzyloxycarbonylaminoethylthio(thiocarbonyl)]thioazetidin-2-one

Product 1

HCID 13175766(3S, 4R)-3-[(R)-1-t-Butyldimethylsilyloxyethyl]-4-[1-methyl-2p-nitrobenzyloxycarbonylaminoethylthio(thiocarbonyl)]thio-1-[1-(p-nitrobenzyloxycarbonyl)triphenylphosphoranylidenemethyl]azetidin-2-oneYield 54.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 5 ml of tetrahydrofuran were dissolved 223 mg (0.285 mmole) of (3S, 4R)-3 -[(R)-1-t-butyldimethylsilyloxyethyl]-1-[1-hydroxy-1-(p-nitrobenzyloxycarbonyl)methyl]-4-[1-methyl-2-p-nitrobenzyloxycarbonylaminoethylthio(thiocarbonyl)]thioazetidin-2-one. To the resulting solution were added, in turn, 34 mg (0.31 mmole) of 2,6-lutidine and 37 mg (0.31 mmole) of thionyl chloride at 31 15° C. The mixture was stirred at that temperature for 15 minutes. After the addition of a further 60 mg (0.56 mmole) of 2,6-lutidine and 183 mg (0.70 mmole) of triphenylphosphine, the mixture was stirred at 65° C. in a stream of nitrogen for 35 hours. Upon completion of the reaction, the mixture was diluted with ethyl acetate, washed with water and dried. The solvent was distilled off and the resulting residue was subjected to column chromatography through 10 g of silica gel eluted with a 15-20% v/v solution of ethyl acetate in benzene to give 159 mg (yield 54% ) of the desired product as a yellow oil.

Workup

  1. stirringthe mixture was stirred at 65° C. in a stream of nitrogen for 35 hours
  2. customUpon completion of the reaction
  3. washwashed with water
  4. customdried
  5. distillationThe solvent was distilled off
  6. washeluted with a 15-20% v/v solution of ethyl acetate in benzene

Sources & evidence

ORD record
ord-cad57fcc2d3542fe8ab0aa9347ba3b4a
Source dataset
uspto-grants-1983_07
Patent number
US04395418

Reaction notes

Loading…