Methyl acetoacetate → Methyl 3-oxo-6-heptenoate

HRID 465513Notes

Reaction equation

HRID 465513 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[CH2:9](Br)[CH:10]=[CH2:11].[H-].[Na+].Br[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1>>[O:4]=[C:3]([CH2:5][CH2:11][CH:10]=[CH2:9])[CH2:2][C:1]([O:7][CH3:8])=[O:6].[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH:9]=[CH:10][CH2:11][CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])[CH:17]=1

Participants

6

Reactant 4

HCID 7757Methyl acetoacetateHCID 7841Allyl bromideHCID 122863-BromopyridineHCID 24758Sodium hydride

Product 2

HCID 366065Methyl 3-oxo-6-heptenoateHCID 54379582Methyl 7-(3-pyridyl)-3-oxo-hept-6-enoate

Procedure

Methyl 3-oxo-hept-6-enoate is prepared e.g. by condensation of methyl acetoacetate with allyl bromide in the presence of sodium hydride. Condensation with 3-bromo-pyridine under conditions of a Heck condensation yields methyl 7-(3-pyridyl)-3-oxo-hept-6-enoate. Condensation thereof with e.g. 4-iodobutyronitrile in the presence of sodium hydride leads to methyl 2-(3-cyanopropyl)-7-(3-pyridyl)-3-oxo-hept-6-enoate. Decarboxylation thereof e.g. with sodium chloride in dimethylsulfoxide/water yields 10-(3-pyridyl)-6-oxo-dec-9-enenitrile. This is subjected to Wittig type condensation with triethyl phosphonoacetate followed by hydrogenation e.g. with Raney nickel catalyst in e.g. methanol/ammonia to yield ethyl 7-(3-pyridyl)-3-(5-aminopentyl)-hept-2-enoate. Further hydrogenation with Pd/C catalyst yields the amine of formula XII wherein Het represents 3-pyridyl, A represents 1,5-pentylene, B represents 1,4-butylene and M represents methylene, as the ethyl ester.

Workup

  1. customunder conditions of a Heck condensation

Sources & evidence

ORD record
ord-1f0b0df54c974da1b97ffbda27c056f9
Source dataset
uspto-grants-1992_10
Patent number
US05153214

Reaction notes

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