Dimethylformamide → Tert-butyl 4-formyl-2-methylbenzoate
Reaction equation
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][C:8]=1[CH3:14])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CN(C)[CH:23]=[O:24]>O1CCCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10]([CH:23]=[O:24])=[CH:9][C:8]=1[CH3:14])([CH3:4])([CH3:3])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -95 °C
Procedure
A solution of 4-bromo-2-methyl-benzoic acid tert-butyl ester (Example 4.1) (75 g) in dry tetrahydrofuran (750 ml) was cooled to −100° C. A solution of butyl lithium (1.6M in hexane) (163 ml) was added dropwise at −100° C. Dimethylformamide (“DMF”) (1.14 ml) was added at −100° C. The reaction mixture was stirred at −95° C. for 75 minutes. The reaction was quenched by addition of aqueous ammonium chloride (saturated) (8 ml) at −90° C. The mixture was stirred for 10 minutes at −90° C., warmed to 0° C. and poured onto a mixture of ice and water. The mixture was allowed to warm to ambient temperature and then extracted twice with ethyl acetate. The combined organic phases were washed with water, dried over sodium sulfate, and concentrated to give 4-formyl-2-methyl-benzoic acid tert-butyl ester (60.3 g) as yellow oil. 1H-NMR (CDCl3, 400 MHz): 10.03 (s, 1H), 7.93 (d, 1H), 7.75 (m, 2H), 2.65 (s, 3H), 1.65 (s, 9H).
Workup
- customThe reaction was quenched by addition of aqueous ammonium chloride (saturated) (8 ml) at −90° C
- stirringThe mixture was stirred for 10 minutes at −90° C.
- temperaturewarmed to 0° C.
- additionpoured onto a mixture of ice and water
- temperatureto warm to ambient temperature
- extractionextracted twice with ethyl acetate
- washThe combined organic phases were washed with water
- dry with materialdried over sodium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-833add408d3c43a08aa89a082e2c6415
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216973B2
Reaction notes
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