Methyl iodide → HCID 13080739, compound

To an anhydrous tetrahydrofuran (1370 mL) suspension of (4-carboxybutyl)triphenylphosphonium bromide (180.3 g) was added potassium t-butoxide (91.4 g) over 6 minutes while the mixture was stirred on a water bath. The mixture was stirred for 3 hours, and then to the reaction mixture was added dropwise an anhydrous tetrahydrofuran (130 mL) solution of the compound 2 (70.7 g) over 5 minutes. The mixture was further stirred at room temperature for 1 hour, the reaction mixture was then poured into ice water (4.2 L), and a 10% aqueous oxalic dihydrate solution (about 195 mL) was added to adjust pH to 5 to 6. The reaction mixture was extracted (1 L×3 times) with a mixed liquid of hexane (500 mL) and ethyl acetate (500 mL), and the organic layers were combined, and washed with a saturated saline (500 mL). The mixture was dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a crude product (161.1 g), which was dissolved in acetone (260 mL). To this solution were added potassium carbonate (34.0 g) and methyl iodide (20 mL), and the mixture was stirred at room temperature for 14 hours, and further refluxed for 1 hour. After allowing to cool to room temperature, an insoluble solid was filtered away, and the filtrate was concentrated under reduced pressure to about ½ of the original volume. To this solution was added water (750 mL), and the mixture was extracted with a mixed liquid of hexane (250 mL) and ethyl acetate (250 mL). The extract was washed with a saturated saline (500 mL), and washing water and the aqueous layer were combined, and extracted again with ethyl acetate (200 mL). The organic layers were combined, dried with anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to obtain a titled compound (79.6 g) having the following physical property values.

1. stirringThe mixture was stirred for 3 hours
2. stirringThe mixture was further stirred at room temperature for 1 hour
3. extractionThe reaction mixture was extracted (1 L×3 times) with a mixed liquid of hexane (500 mL) and ethyl acetate (500 mL)
4. washwashed with a saturated saline (500 mL)
5. dry with materialThe mixture was dried with anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto obtain a crude product (161.1 g), which
8. stirringthe mixture was stirred at room temperature for 14 hours
9. temperaturefurther refluxed for 1 hour
10. filtrationan insoluble solid was filtered away
11. concentrationthe filtrate was concentrated under reduced pressure to about ½ of the original volume
12. additionTo this solution was added water (750 mL)
13. extractionthe mixture was extracted with a mixed liquid of hexane (250 mL) and ethyl acetate (250 mL)
14. washThe extract was washed with a saturated saline (500 mL)
15. washwashing water
16. extractionextracted again with ethyl acetate (200 mL)
17. dry with materialdried with anhydrous sodium sulfate
18. concentrationconcentrated
19. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

ORD record

ord-2c6b630e96c74fd5954da7498ae2ef10

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150537B2