tert-Butanol → HCID 178428488, compound

Temperature

75 °C

A flask was charged with (2-Formyl-phenyl)-carbamic acid tert-butyl ester (8.8 g, 0.040 mol), 2-(4-Amino-2-methyl-phenyl)-propane-1,3-diamine (10.0 g, 0.056 mol), t-butanol (177 mL), and N,N-dimethylformamide (53 mL) and purged well with nitrogen. The mixture was stirred at 75° C. for at least 3 h. To the cooled mixture were added anhydrous potassium carbonate (16.6 g) and iodine (12.2 g). The batch was stirred at 80° C. for 10 h. The cooled mixture was filtered through a celite pad (4.4 g) and the filter cake was rinsed with methanol (177 mL). The filtrate and wash were diluted with toluene (88 mL) and concentrated to dryness under reduced pressure. The residue was stirred with aqueous 15 wt % sodium thiosulfate pentahydrate (88 mL) and saturated aqueous sodium chloride (44 mL) for 1 h at ambient temperature. The resulting mixture was extracted with CH2Cl2 (2×177 mL). The separated organic layer was dried over anhydrous magnesium sulfate (4.4 g), filtered, and concentrate to dryness in vacuo. The concentrate (20 g) was dissolved with methanol (20 mL) and loaded onto a KP-Sil samplet (34 g). The sample was allowed to dry before loading it into a Biotage KP-Sil SNAP cartridge (340 g). A Biotage unit was used to elute the cartridge with a ethyl acetate-hexane gradient (0% to 90%). Clean fractions were collected, combined, and concentrated to dryness under reduced pressure to provide the title compound as a yellow solid (1.6 g, 13% yield).

1. custompurged well with nitrogen
2. additionTo the cooled mixture were added anhydrous potassium carbonate (16.6 g) and iodine (12.2 g)
3. stirringThe batch was stirred at 80° C. for 10 h
4. filtrationThe cooled mixture was filtered through a celite pad (4.4 g)
5. washthe filter cake was rinsed with methanol (177 mL)
6. washThe filtrate and wash
7. additionwere diluted with toluene (88 mL)
8. concentrationconcentrated to dryness under reduced pressure
9. stirringThe residue was stirred with aqueous 15 wt % sodium thiosulfate pentahydrate (88 mL) and saturated aqueous sodium chloride (44 mL) for 1 h at ambient temperature
10. extractionThe resulting mixture was extracted with CH2Cl2 (2×177 mL)
11. dry with materialThe separated organic layer was dried over anhydrous magnesium sulfate (4.4 g)
12. filtrationfiltered
13. concentrationconcentrate to dryness in vacuo
14. concentrationThe concentrate (20 g)
15. dissolutionwas dissolved with methanol (20 mL)
16. customto dry
17. washto elute the cartridge with a ethyl acetate-hexane gradient (0% to 90%)
18. customClean fractions were collected
19. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-9b35510ec2f24535acadaa91f36ee1d2

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365575B2