Methanol → Methyl 2-(5-broMopyridin-2-yl)acetate

HRID 220169Notes

Reaction equation

HRID 220169 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[N:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[CH3:16][O:10][C:9](=[O:11])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 46238459(5-Bromopyridin-2-yl)acetic acid

Product 1

HCID 53419526Methyl 2-(5-broMopyridin-2-yl)acetate

Procedure

Key building block 2-(5-bromo-pyridin-2-yl)-5-chloro-pentanoic acid (XII) can be prepared according to Scheme 8. Starting with commercially available 5-bromo-2-iodo-pyridine (XXXV), copper-catalyzed reaction with malonic acid diethyl ester furnishes 2-(5-bromo-pyridin-2-yl)-malonic acid diethyl ester (XXXVI). Hydrolysis and decarboxylation under basic conditions gives (5-bromo-pyridin-2-yl)-acetic acid (XXXVII), which subsequently can undergo nucleophilic acyl substitution with thionyl chloride in methanol to provide (5-bromo-pyridin-2-yl)-acetic acid methyl ester (XXXVIII). Deprotonation of XXXVIII with strong base followed by alkylation with 1-bromo-3-chloropropane gives 2-(5-bromo-pyridin-2-yl)-5-chloro-pentanoic acid methyl ester (XXXIX), which can then be hydrolyzed under aqueous basic conditions to furnish key building block 2-(5-bromo-pyridin-2-yl)-5-chloro-pentanoic acid (XII).

Workup

  1. customHydrolysis and decarboxylation under basic conditions

Sources & evidence

ORD record
ord-44ba62b900434a189319d8b637d8c795
Source dataset
uspto-grants-2012_06
Patent number
US08202866B2

Reaction notes

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