Diethyl Ether → Di-tert-butyl dicarbonate

HRID 2211026

Reaction equation

HRID 2211026 reaction equation
[C:1]([O:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(C)(C)C.[C:13]([O:17]C(Cl)=O)([CH3:16])([CH3:15])[CH3:14].N1C(C)=CC=CC=1C.Cl[C].CC[O:33]CC>ClCCl.C(N(CC)CC)C.N1C=CC=CC=1>[C:13]([O:17][C:1]([O:5][C:6]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:12])=[O:33])([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 5

HCID 3283Diethyl EtherHCID 79372,6-LutidineHCID 9920397Tert-butyl ChloroformateHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) esterHCID 178462445HCID 178462445, compound

Product 1

HCID 90495Di-tert-butyl dicarbonate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

The 3-(N-t-butyloxycarbonyl-1'-N-methylaminoethyl)pyrrolidines (60, 61, 62, 63) were prepared by reacting the amines (8-11) with a t-butyloxycarbonyl transfer agent such as di-t-butylcarbonate or t-butyloxycarbonyl chloride or the like in the presence of an acid scavenger such as a tertiary amine including pyridine, lutidine, triethylamine and the like either with or without an inert solvent such as an ether or chlorocarbon in a temperature range of room temperature to the reflux temperature of the reaction mixture for 6-72 hours, preferable in dichloromethane and di-t-butylcarbonate at ambient temperature for 12-24 hours to give the 3-(N-t-butyloxycarbonyl-1'-aminoethyl)-1-(S-α-methylbenzyl)pyrrolidin-5-ones, 48, 49, 50, 51, Equation 14. The two amides were removed by reacting the pyrrolidin-5-ones (48-51) with a hydride reducing agent in an inert solvent. The preferred method was with lithium aluminum hydride in THF at reflux for 12-24 hours giving the individual diastereomeric pyrrolidines, 52, 53, 54, 55, Equation 15. The reduced pyrrolidines, 52-55, could be protected by reacting the 3-N-methyl-1'-aminomethyl moiety with a t-butyloxycarbonyl transfer agent such as di-t-butylcarbonate or t-butyloxycarbonyl chloride or the like in the presence of an acid scavenger such as a tertiary amine including pyridine, lutidine, triethylamine and the like either with or without an inert solvent such as an ether or chlorocarbon in a temperature range of room temperature to the reflux temperature of the reaction mixture for 6-72 hours, preferably in dichloromethane and di-t-butyldicarbonate at ambient temperature for 12-24 hours to give the 1-(α-methylbenzyl)-3-(N-t-butyloxycarbonyl-1'-N-methylaminoethyl)pyrrolidines, 56, 57, 58, 59, Equation 16. The 3-(N-t-butyloxycarbonyl-1'-N-methylaminoethyl)pyrrolidines, 56-59 were de-α-methylbenzylated via hydrogenolysis using varying percentages of palladium on an inert support such as carbon, alumina, silica, or the like, preferably 20% palladium on carbon in an inert solvent such as methanol, ethanol, THF, or ethyl acetate. This provides the 3-(1'-N-t-butoxycarbonyl-1'-N-methylaminoethyl)pyrrolidines, 60, 61, 62, 63 (Equation 17) in a form suitable for coupling with a quinolone or naphthyridone nucleus.

Workup

  1. customThe two amides were removed
  2. temperatureat reflux for 12-24 hours
  3. customgiving the individual diastereomeric pyrrolidines, 52, 53, 54, 55, Equation 15

Sources & evidence

ORD record
ord-d44a3c8abe8a4721a16f3e002d2a1af0
Source dataset
uspto-grants-1995_10
Patent number
US05461165

Linked notes

Loading…