Methyl 3-(bromomethyl)benzoate → HCID 10419823, compound

To a solution of methyl 3-bromomethylbenzoate (6.9 g, 30 mmol; Lancaster) in dry acetone (10 mL) was added via dropwise addition a solution of thiourea (2.28 g, 30 mmol) in dry acetone (40 mL) at room temperature. After 15 minutes the precipitated thiouronium salt was collected by filtration; the solids were washed with acetone and dried. The thiouronium salt was dissolved in H2O (65 mL) and the pH was adjusted to 10.5 by the addition of 10% NaOH. The mixture was refluxed for 2 hours. After cooling to room temperature the solution was extracted with EtOAc and the organic layer was discarded. The aqueous solution was acidified to pH 1.5 and extracted three times with EtOAc. The organic extracts were dried (MgSO4), filtered and the solvent evaporated. The crude acid was then dissolved in anhydrous MeOH (125 mL), cooled to 0° C., and dry HCl gas was bubbled through the solution for 30 minutes. The reaction was then left for two days at room temperature. The mixture was concentrated in vacuo and the product was purified by flash column chromatography (silica, 5% EtOAc in hexane) providing a colorless oil: 1H NMR (250 MHz, CDCl3) δ8.00 (s, 1H, 2-phenyl), 7.91 (d, J=7.6 Hz, 1H, 6-phenyl), 7.52 (d, J=7.6 Hz, 1H, 4-phenyl), 7.39 (dd, J=7.6 Hz, 1H, 5-phenyl), 3.92 (s, 3H, methyl ester), 3.78 (d, J=7.7 Hz, 2H, SCH2), 1.79 (t, J=7.7 Hz, 1H, SH).

1. filtrationAfter 15 minutes the precipitated thiouronium salt was collected by filtration
2. washthe solids were washed with acetone
3. customdried
4. dissolutionThe thiouronium salt was dissolved in H2O (65 mL)
5. additionthe pH was adjusted to 10.5 by the addition of 10% NaOH
6. temperatureThe mixture was refluxed for 2 hours
7. extractionwas extracted with EtOAc
8. extractionextracted three times with EtOAc
9. dry with materialThe organic extracts were dried (MgSO4)
10. filtrationfiltered
11. customthe solvent evaporated
12. dissolutionThe crude acid was then dissolved in anhydrous MeOH (125 mL)
13. temperaturecooled to 0° C.
14. customdry HCl gas was bubbled through the solution for 30 minutes
15. concentrationThe mixture was concentrated in vacuo
16. customthe product was purified by flash column chromatography (silica, 5% EtOAc in hexane)
17. customproviding a colorless oil

ORD record

ord-32928277e9554e8f846f58e8123833be

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05633258