Methyl iodide → HCID 21075354, compound

To a solution of 4-fluoro-2-(hydroxymethyl)benzoic acid (Preparation 36, 0.185 g, 0.001087 mol) in tetrahydrofuran (5.0 mL) was added sodium hydride (0.110 g, 0.0028 mmol, 60% in mineral oil) portion wise. The reaction was stirred for 15 minutes at room temperature under nitrogen. Then 0.17 mL iodomethane (0.17 mL, 0.00272 mol) was added and the reaction mixture stirred at room temperature under nitrogen for 16 hours. The reaction was quenched with an aqueous solution of hydrochloric acid (2.0M, 10.0 mL) and product was extracted with ethyl acetate (15.0 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dimethyl sulfoxide (3.0 mL), then potassium carbonate (0.170 g, 0.00123 mol) and iodomethane (0.17 mL, 0.00272 mol) were added. The reaction mixture was stirred at 60° C. under nitrogen for 2 hours. The reaction was diluted with ethyl acetate (15.0 mL) and washed three times with water (15.0 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. Title compound was isolated after purification using silica gel column chromatography eluting with 0-10% EtOAc in heptane as a colourless oil (0.135 g, 0.000681, 67% yield).

1. stirringthe reaction mixture stirred at room temperature under nitrogen for 16 hours
2. customThe reaction was quenched with an aqueous solution of hydrochloric acid (2.0M, 10.0 mL) and product
3. extractionwas extracted with ethyl acetate (15.0 mL)
4. dry with materialThe organic phase was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in dimethyl sulfoxide (3.0 mL)
8. stirringThe reaction mixture was stirred at 60° C. under nitrogen for 2 hours
9. washwashed three times with water (15.0 mL)
10. dry with materialThe organic phase was dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-63dc30bb27534a1e9091ea3825d0a42b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08685977B2