Methanol → Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate

HRID 897380Notes

Reaction equation

[Br:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11]([C:13]1[C:22]([OH:23])=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[N:20]2)=[CH:15][N:14]=1)=[O:12].CO.CO.O>C(Cl)(Cl)Cl>[CH3:9][O:10][C:11]([C:13]1[C:22]([OH:23])=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[N:20]2)=[C:15]([Br:1])[N:14]=1)=[O:12]

Participants

Conditions

Temperature: 35 °C

Procedure

N-bromosuccinimide (7.83 g, 44.0 mmol) was added to a solution of 8-hydroxy-1,6-naphthyridine-7-carboxylic acid methyl ester (5, 8.17 g, 40.0 mmol) in chloroform (32 mL) over 20 min maintaining the temperature at 20-50° C. and the mixture was aged for 30 min at 50° C. The mixture became a thick, stirrable slurry and HPLC analysis indicated <2% starting material remaining. The mixture was cooled to 30° C. over 15 min. MeOH (64 mL) was added over 30 min then a 1:1 mixture of MeOH-water (64 mL) was added over 30 min. The mixture was cooled to −40° C. over 30 min and aged at −40° C. for 30 min. The cold mixture was filtered and the solid was washed with 1:1 MeOH:water (100 mL) at 10-20° C. The off white crystalline solid was dried under a stream of nitrogen to provide 10.48 g (93% yield) of 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylic acid methyl ester (6).

Workup

temperatureThe mixture was cooled to 30° C. over 15 min
additionwas added over 30 min
temperatureThe mixture was cooled to −40° C. over 30 min
waitaged at −40° C. for 30 min
filtrationThe cold mixture was filtered
washthe solid was washed with 1:1 MeOH
customat 10-20° C
customThe off white crystalline solid was dried under a stream of nitrogen

Sources & evidence

ORD record: ord-c8c241fb7c574a11bb6b423178eb56fa
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06921759B2

Reaction notes

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