Methanol → Methyl 4-(bromomethyl)benzoate
Reaction equation
[Br:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1.OS(O)(=O)=O.[CH3:17]O>>[Br:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([O:9][CH3:17])=[O:8])=[CH:5][CH:4]=1Participants
Procedure
Intermediate 1 was prepared as shown in Scheme 2. Esterification of 4-bromomethylbenzoic acid 4 (25 grams) was carried out in refluxing methanol (500 ml) in the presence of concentrated H2SO4 (5 ml) to yield methyl 4-bromomethylbenzoate 5. TLC (thin layer chromatography) monitoring of the reaction mixture showed formation, over time, of a side-product (about 15-20%), which according to 1H-NMR analysis, was identified as methyl 4-methoxymethylbenzoate. The mixture of methyl 4-bromomethylbenzoate 5 and the side-product (4.56 grams; 1 equiv) was reacted with commercially available 4-boc-aminopiperidine 6 (Aldrich™) (4.0 grams) in 100 ml of DCM or 100 ml of methanol in the presence-of potassium carbonate (4.14 grams; 1.5 equiv) at room temperature to yield compound 7. Reaction in methanol afforded compound 7, as identified by 1H NMR, in 72% yield compared to 57% obtained with DCM.
Sources & evidence
- ORD record
- ord-3b8c7230e10f4a43a761f509d1cfd83e
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07585866B2
Reaction notes
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