Preparation of n-protected-3-pyrrolidine-lactam substituted phosphonium salts
AssigneeBasilea Pharmaceutica AG
InventorMark Rogers-Evans
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Abstract
New process for the preparation of bipyrrolidinyl compounds of formula I wherein * signifies an asymmetric centre with an (R) or (S) configuration and X represents chlorine, bromine or iodine. The compounds of formula I are important building blocks for the production of useful products in the chemical and in the pharmaceutical industry. In particular they are useful for the production of antibacterial substances for example like vinylpyrrolidinone-cephalosporin derivatives. 1
Claims12
A process for the preparation of bipyrrolidinyl compounds of formula I
- 14
- wherein * signifies an asymmetric center with an (R) or (S) configuration and X represents chlorine, bromine or iodine;
- comprises
- step 1) coupling the compound of formula II
- 15
- wherein * is as defined above with a compound of formula X(CH2)2CH(X)COX
- wherein X is independently of each other chlorine, bromine or iodine;
- and subsequent cyclization in the presence of a base to obtain a compound of formula III
- 16
- wherein * and X are as defined above;
- step 2) reacting the compound of formula III with triphenylphosphine to obtain the phosphonium salt of formula IV
- 17
- wherein * and X are as defined above;
- and
- step 3) reacting the phosphonium salt of formula IV with di-tert.-butyl-dicarbonate under hydrogenation conditions to obtain the compounds of formula I.
The compound of formula IIIa (R)-(1′-benzyl-3-bromo-[1,3′]bipyrrolidinyl-2-one).
The compound of formula IVa (1′-benzyl-2-oxo-[1,3′]-(R)-bipyrrolidinyl-3-(R,S)-yl)-triphenyl-phosphonium bromide.
Use of compounds of formula II-VII for the preparation of compounds of formula VIII
- 24
- wherein R3 is a hydroxy protecting group, R4 is a carboxylic acid protecting group, * is as defined above and R5 is an amino protecting group or a group of formula B
- 25
- wherein R6 is an alkyl group.
Dependencies are inferred from the claim text.