Dimethylformamide → HCID 67464161, compound

Temperature

-78 °C

Methyl 4-(cyanomethoxy)-2-methoxy-benzoate (960 mg, 4.34 mmol) was dissolved in tetrahydrofuran (1 mL) and N,N-dimethylformamide (4 mL). Sodium hydride (521 mg, 13.0 mmol) was added and the reaction mixture was allowed to stir for 5 min. Iodomethane (1.35 mL, 21.7 mmol) was added and the reaction mixture was allowed to stir for 10 min. The reaction mixture was quenched with water and extracted with ethyl acetate. The ethyl acetate was dried over sodium sulfate, filtered and evaporated to dryness. The crude material was then dissolved in tetrahydrofuran (10 mL) and was cooled to −78° C. under an atmosphere of argon. LDA (2.2 mL of 2.0 M, 4.4 mmol) was added and the reaction mixture was stirred at −78° C. for 45 minutes. Iodomethane (1.35 mL, 21.7 mmol) was added and the reaction mixture was allowed to slowly warm to room temperature. The reaction mixture was evaporated to dryness, and then partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed two times with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and evaporated to dryness. The crude product was then purified on 40 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes to give methyl 4-(1-cyano-1-methyl-ethoxy)-2-methoxy-benzoate (31%). ESI-MS m/z calc 249.1. found 250.3 (M+1)+. Retention time: 1.59 minutes (3 min run).

1. stirringto stir for 10 min
2. customThe reaction mixture was quenched with water
3. extractionextracted with ethyl acetate
4. dry with materialThe ethyl acetate was dried over sodium sulfate
5. filtrationfiltered
6. customevaporated to dryness
7. dissolutionThe crude material was then dissolved in tetrahydrofuran (10 mL)
8. stirringthe reaction mixture was stirred at −78° C. for 45 minutes
9. temperatureto slowly warm to room temperature
10. customThe reaction mixture was evaporated to dryness
11. custompartitioned between ethyl acetate
12. washThe organic layer was washed two times with a saturated aqueous solution of sodium chloride
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. customevaporated to dryness
16. customThe crude product was then purified on 40 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes

ORD record

ord-477106361c0a488ca098454dba15b9b2

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598164B2