Sodium Hydroxide → 2-[4-Chloro-2-(pyrrolidine-1-sulfonyl)-phenoxy]-2-methyl-propionic acid

Temperature

25 °C

The product of Example 44B (1.0 g, 3.82 mmol) and 1,1,1-trichloro-2-methyl-2-propanol hydrate (1.832 g, 10.32 mmol) were dissolved in acetone (8.5 mL). Powdered NaOH (0.47 g. 11.75 mmol) was added with cooling. The resulting mixture was stirred for 1.5 hr at 25° C. A second batch of powdered NaOH (0.47 g) was added and stirred for another 1.5 hrs. The last batch of powdered NaOH (0.47 g) was then added along with acetone (2.5 mL). The resulting mixture was stirred for 15 hrs at 25° C. Acetone was added and the solution was filtered. The resulting solution was concentrated. Water (3 mL) was added and concentrated HCl was added to acidify the mixture, which was extracted with toluene, dried and concentrated. The residue was chromatographed on silica gel. Eluting with CH2Cl2 gave 380 mg recovered starting material. Changing to 5% MeOH in ethyl acetate gave the title compound (357 mg, 27% yield).

1. temperaturewith cooling
2. stirringstirred for another 1.5 hrs
3. stirringThe resulting mixture was stirred for 15 hrs at 25° C
4. filtrationthe solution was filtered
5. concentrationThe resulting solution was concentrated
6. additionWater (3 mL) was added
7. additionconcentrated HCl was added
8. extractionwas extracted with toluene
9. customdried
10. concentrationconcentrated
11. customThe residue was chromatographed on silica gel
12. washEluting with CH2Cl2
13. customgave 380 mg
14. customrecovered

ORD record

ord-a9f62e3a063e459e9dbc1080e443fac2

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716345B2