Dimethylformamide → Tert-butyl 4-formyl-2-methylbenzoate

HRID 874211Notes

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

Conditions

Temperature: -95 °C

Procedure

A solution of 4-bromo-2-methyl-benzoic acid tert-butyl ester (Example I1) (75 g) in dry tetrahydrofuran (750 ml) was cooled to −100° C. A solution of butyl lithium (“BuLi”) (1.6 M in hexane) (163 ml) was added dropwise at −100° C. N,N-Dimethylformamide (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 on 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

customwas cooled to −100° C
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 on 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-b5c3d79de341405b8fb04d6276f14a77
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980892B2

Reaction notes

Loading…