Citric Acid → [5-Fluoro-2-(methoxymethoxy)phenyl]boronic acid

HRID 2069898Notes

Reaction equation

C([Li])CCC.Br[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[O:14][CH2:15][O:16][CH3:17].C[O:19][B:20](OC)[O:21]C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[CH3:17][O:16][CH2:15][O:14][C:8]1[CH:9]=[CH:10][C:11]([F:13])=[CH:12][C:7]=1[B:20]([OH:21])[OH:19]

Participants

Conditions

Temperature: -78 °C

Procedure

A 500 mL round bottom flask was charged with a 1.6 M solution of n-butyllithium in hexanes (100 mL, 0.16 mol) and flushed with nitrogen. The solution was cooled to −78° C. and a solution of 2-bromo-4-fluoro-1-methoxymethoxy-benzene (30.1 g, 0.13 mol) in dry tetrahydrofuran (50 mL) was added dropwise over one hour. The mixture was stirred at −78° C. and then trimethylborate (20 mL, 0.175 mol) was added very slowly via syringe. The reaction was allowed to gradually warm to room temperature and after two hours the mixture was poured into ice. The mixture was acidified to pH 4 with 5% aqueous citric acid and extracted with ethyl acetate (×3). The combined organic extracts were washed with water and brine, dried over MgSO4 and filtered. The solvent was evaporation under reduced pressure and the residue was recrystallized from hexanes give 2-methoxymethoxy-5-fluorophenylboronic acid (18.9 g).

Workup

customflushed with nitrogen
temperatureto gradually warm to room temperature and after two hours the mixture
additionwas poured into ice
extractionextracted with ethyl acetate (×3)
washThe combined organic extracts were washed with water and brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporation under reduced pressure
customthe residue was recrystallized from hexanes

Sources & evidence

ORD record: ord-88c72ecb17284399aa81126a0b152eb9
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299110B2

Reaction notes

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