Diethyl Malonate → diethyl 2-[(4-nitrophenyl)methyl]propanedioate

HRID 531160Notes

Reaction equation

HRID 531160 reaction equation
C(O)CCO.CC1C=CC(S(OCC(CC2C=CC([N+]([O-])=O)=CC=2)COS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1.[N+:41]([C:44]1[CH:51]=[CH:50][C:47]([CH2:48]Br)=[CH:46][CH:45]=1)([O-:43])=[O:42].[C:52]([O:60][CH2:61][CH3:62])(=[O:59])[CH2:53][C:54]([O:56][CH2:57][CH3:58])=[O:55].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[N+:41]([C:44]1[CH:51]=[CH:50][C:47]([CH2:48][CH:53]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:52]([O:60][CH2:61][CH3:62])=[O:59])=[CH:46][CH:45]=1)([O-:43])=[O:42]

Participants

7

Reactant 5

HCID 7761Diethyl MalonateHCID 104421,3-PropanediolHCID 11430Potassium CarbonateHCID 660114-Nitrobenzyl bromideHCID 88592485HCID 88592485, compound

Product 1

HCID 348576diethyl 2-[(4-nitrophenyl)methyl]propanedioateYield 88%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Although PCB-TE2A is a good chelator having an octahedral coordination site with metals like Cu, one of its two pendant arms has to be sacrificed whenever it is conjugated with biomolecules. To keep intact the octahedral coordination structure while allowing further conjugation with biomolecules, introduction of an extra functional group in the backbone is necessary. For this purpose, the inventors have synthesized a suitably tailored nitro-derivative of ditosyl ester of 1,3-propanediol, 25. The precursor was used for the construction of propylene bridge having one extra functionality. The inventors have designed the compound 25 and performed synthesis by condensation of 1 equiv. of 4-nitrobenzyl bromide with 7 equivalent of diethyl malonate in the presence of K2CO3 in acetone to give 23 in 88% yield (Scheme 6). In this reaction a mild base rather than metal alkoxide and excess of diethyl malonate were used in order to prevent the formation of dialkylate product. The diethyl-2-[(4-nitrophenyl)methyl]propanedioate 23 was reduced with sodium borohydride to afford the diol compound 24 in 85% yield. The diol 24 was tosylated by tosyl chloride in pyridine to afford the precursor 25 in 89% yield. According to Scheme 6,2-[(4-nitrophenyl)methyl]propan-1,3-diol bis(4-methylbenzene-sulfonate) (25) was prepared in high overall yield (66%).

Workup

  1. customsynthesis

Sources & evidence

ORD record
ord-1f33610c350b423bb7e79583d17b7a4e
Source dataset
uspto-grants-2016_05
Patent number
US09353120B2

Reaction notes

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