Methyl iodide → Methyl 5-bromoquinoline-8-carboxylate
Reaction equation
[C:1]([O-])([O-])=O.[K+].[K+].CI.[Br:9][C:10]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2>CN(C=O)C>[CH3:1][O:21][C:20]([C:17]1[CH:18]=[CH:19][C:10]([Br:9])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)=[O:22]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 45 °C
Procedure
K2CO3 (61.3 g, 444.0 mmol) and methyl iodide (63.1 g, 444.0 mmol) were added to a stirred suspension of 5-bromoquinoline-8-carboxylic acid (28.0 g, 111.0 mmol) in DMF (250 mL) at r.t. The reaction mixture was heated at 45° C. for 36 h, cooled to r.t, filtered the solids, washed with ethyl acetate (100 mL). The filtrate was diluted with water, extracted with ethyl acetate (3×300 mL) and washed with water (3×100 mL). The ethyl acetate layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate in hexanes (0-20%) to afford methyl-5-bromoquinoline-8-carboxylate as a cream color solid (20.5 g, 70% for 2 steps). 1H NMR (400 MHz, CDCl3) δ 9.07 (dd, J=4.3, 1.5 Hz, 1H), 8.60 (dd, J=8.7, 1.6 Hz, 1H), 7.88 (s, 2H), 7.58 (dd, J=8.6, 4.0 Hz, 1H), 4.05 (s, 3H)
Workup
- temperaturecooled
- filtrationfiltered the solids
- washwashed with ethyl acetate (100 mL)
- additionThe filtrate was diluted with water
- extractionextracted with ethyl acetate (3×300 mL)
- washwashed with water (3×100 mL)
- dry with materialThe ethyl acetate layer was dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by flash column chromatography on silica gel
- washeluting with ethyl acetate in hexanes (0-20%)
Sources & evidence
- ORD record
- ord-2b388fa14944469099f1af67ad49028f
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340509B2
Reaction notes
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