Dimethylformamide → 6-tert-Butyl-5-mercapto-indole-1-carboxylic Acid Tert-Butyl Ester

Temperature

-40 °C

(5-tert-Butyl-4-mercapto-2-methyl-phenyl)-carbamic acid tert-butyl ester (prepared in Example EE; 20 g, 68 mmol) was dissolved in 100 mL of THF, cooled to −40° C., and treated dropwise with sec-butyllithium (1.3 M, 156 mL, 203 mmol). After the addition was complete, the reaction mixture was stirred at −30° C. to −45° C. for 30 minutes. To the mixture was added DMF (14.8 g, 203.39 mmol), and the solution was stirred at −35° C. for 30 minutes. The reaction mixture was slowly warmed to room temperature and was quenched with saturated NH4Cl solution. EtOAc (200 mL) was added; the organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was dissolved in 100 mL of THF and 2 mL of concentrated HCl and stirred at room temperature for 1 hour. The solution was diluted with EtOAc, washed with NaHCO3 solution and brine, and dried (MgSO4). The crude product was purified by flash silica gel chromatography to give the title compound. MS(APCI): 304 (M−H).

1. additionAfter the addition
2. stirringthe solution was stirred at −35° C. for 30 minutes
3. temperatureThe reaction mixture was slowly warmed to room temperature
4. customwas quenched with saturated NH4Cl solution
5. additionEtOAc (200 mL) was added
6. washthe organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in 100 mL of THF
10. stirring2 mL of concentrated HCl and stirred at room temperature for 1 hour
11. additionThe solution was diluted with EtOAc
12. washwashed with NaHCO3 solution and brine
13. dry with materialdried (MgSO4)
14. customThe crude product was purified by flash silica gel chromatography

ORD record

ord-6a3ea713506c46b18b9f15a88d0395d4

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528510B1