Isopropyl iodide → HCID 43140622, compound

Hydrazine hydrate (3.29 ml, 66.9 mmol) was added dropwise to a solution of 2-bromo-5-(chlorosulfonyl) benzoic acid (Preparation 22, 10.0 g, 33.4 mmol) in THF (100 mL) at 0° C. Once the addition was complete the mixture was allowed to warm to room temperature and the solid was collected by filtration. The solid was washed with heptane (3×20 mL) and dried under vacuum at 50° C. for 18 hours. The solid was dissolved in EtOH (100 mL) and NaOAc (16.4 g, 198 mmol) and 2-iodopropane (16.7 mL, 165 mmol) were added. The mixture was heated to reflux for 16 hours, cooled to room temperature and the solvent was evaporated under reduced pressure to leave an off-white solid. The solid was partitioned between EtOAc (50 mL) and 1M NaOH (100 mL). The aqueous layer was separated, acidified to pH=1 with 2M HCl and extracted with EtOAc (3×50 mL). The combined EtOAc extracts were dried over MgSO4 and the solvent was evaporated under reduced pressure to leave an orange oil. The oil was purified by silica gel column chromatography eluting with MeOH/CH2Cl2/AcOH 5:95.5:0.5 followed by a further chromatography eluting with heptanes/EtOAc 4:1 to give the title compound as a white solid 8% yield, 0.78 g.

1. additionOnce the addition
2. filtrationthe solid was collected by filtration
3. washThe solid was washed with heptane (3×20 mL)
4. customdried under vacuum at 50° C. for 18 hours
5. dissolutionThe solid was dissolved in EtOH (100 mL)
6. temperatureThe mixture was heated
7. temperatureto reflux for 16 hours
8. temperaturecooled to room temperature
9. customthe solvent was evaporated under reduced pressure
10. customto leave an off-white solid
11. customThe solid was partitioned between EtOAc (50 mL) and 1M NaOH (100 mL)
12. customThe aqueous layer was separated
13. extractionextracted with EtOAc (3×50 mL)
14. dry with materialThe combined EtOAc extracts were dried over MgSO4
15. customthe solvent was evaporated under reduced pressure
16. customto leave an orange oil
17. customThe oil was purified by silica gel column chromatography
18. washeluting with MeOH/CH2Cl2/AcOH 5:95.5:0.5
19. washeluting with heptanes/EtOAc 4:1

ORD record

ord-97170949e12e4e758c6e7b2c59013b04

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952008B2