Dimethylformamide → Tert-butyl 3,5-difluoro-4-formylbenzoate

HRID 1627374Notes

Reaction equation

C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:15]=[C:16]([CH:24]=[C:25]([F:27])[CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].CN([CH:31]=[O:32])C>C1COCC1.CCOC(C)=O.O.CC(O)=O>[F:13][C:14]1[CH:15]=[C:16]([CH:24]=[C:25]([F:27])[C:26]=1[CH:31]=[O:32])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of diisopropylamine (5 mL, 35.5 mmol, 1.2 eq) in THF (100 mL, anhyd) was slowly added BuLi (1.6M in hexanes, 20 mL, 32.3 mmol, 1.1 eq) at below 0° C. After addition was completed, the solution was cooled to −78° C. and then charged dropwise with a solution of tert-butyl 3,5-difluorobenzoate (6.3 g, 29 mmol) in THF (50 mL, anhyd) over 1 h. The resulting solution was stirred for another 2 h at −78° C. Next anhyd DMF (2.5 mL, 32.3 mmol, 1.1 eq) was added dropwise and, after 30 min, AcOH (4 mL) and water were added successively to quench the reaction. The reaction mixture was warmed to room temperature and diluted with EtOAc (100 mL). The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-formylbenzoate (5.8 g, 83%) as a white solid.

Workup

customat below 0° C
additionAfter addition
customto quench
customthe reaction
temperatureThe reaction mixture was warmed to room temperature
washThe organic layer was washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography (Hex/EtOAc=4:1)

Sources & evidence

ORD record: ord-d1d98d22549c43b9a04f124bd1a84a7f
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785488B2

Reaction notes

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