Dichloromethane → Diisopropylamine
Reaction equation
[F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].FC(F)(F)S(Cl)(=O)=O.C([N:26]([CH2:29][CH3:30])CC)C.[CH2:31](Cl)Cl.O1[CH2:38][CH2:37][CH2:36]C1>>[CH:37]([NH:26][CH:29]([CH3:30])[CH3:31])([CH3:38])[CH3:36].[F:1][C:2]([F:15])([F:14])[S:3]([O-:6])(=[O:5])=[O:4]Participants
Procedure
The starting material for the synthesis is the readily available 3-hydroxycephem 1 (M=p-methoxy benzyl or benzhydryl). As shown in scheme A, reaction of 1 with a suitable trifluoromethanesulfonyl source, such as trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride or the like, in the presence of an organic nitrogen base, such as triethylamine, diisopropyl amine and the like in an aprotic solvent such as methylene chloride or tetrahydrofuran gives the triflouromethanesulfonate at the 3-position, as a stable isolable solid 2. Reaction of 2 with the sodium salt of a suitable heteroaryl thiol, prepared by the reaction of a reagent such as sodium hydride or sodium hexamethyldisilazide with the thiol, in a non-polar solvent or solvent mixture at -20° C. to room temperature, gives the desired addition product 4, as a mixture of the Δ2 and Δ3 isomers. The desired Δ3 isomer is separated by fractional crystallization or by chromatography.
Sources & evidence
- ORD record
- ord-0e8c1277bd3a48a08a76d1a8dc4b79d8
- Source dataset
- uspto-grants-1996_03
- Patent number
- US05498777
Reaction notes
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