Tert-Butylamine → HCID 67515804, compound

Temperature

70 °C

Methyl 5,6,7,8-tetrahydroquinoline-5-carboxylate-1-oxide (2.05 g, 9.89 mmol) and t-butyl amine (5.22 ml, 49.5 mmol) were dissolved in benzotrifluoride (50 ml) and cooled with an ice bath. The p-toluenesulfonic anhydride (6.46 g, 19.79 mmol) was added portionwise keeping the reaction's internal temperature below 5° C. The reaction was monitored and after 10 mins. when the LC-MS showed M+1=263 and 207 (M-56) at 1.20 indicating formation of intermediate methyl 2-(tert-butylamino)-5,6,7,8-tetrahydroquinoline-5-carboxylate. Trifluoroacetic acid (10 ml) was then added to the reaction mixture and heated at 70° C. for 5 hrs. The reaction was cooled and evaporated to dryness. The residue was taken up with water and the pH was adjusted to pH ˜8 with 5N NaOH. The reaction was extraction with DCM 2×. The combined DCM layers were washed with brine and dried over Na2SO4, filtered and evaporated to dryness. The residue was chromatographed through a 80 g ISCO Redi-sep column and eluted with solvent system of 5%(10% NH4OH in MeOH)/DCM to yield methyl 2-amino-5,6,7,8-tetrahydroquinoline-5-carboxylate. 1H-NMR (600 MHz, CDCl3): δ ppm 7.27 (d, J=8.3 Hz, 1H), 6.35 (d, J=8.3 Hz, 1H), 4.40 (b, 2H), 3.73 (s, 3H), 3.70 (t, J=6.9 Hz, 1H), 2.68-2.82 (m, 2H) 2.12-2.17 (m, 1H), 1.93-2.12 (m, 2H), 1.81-1.86 (m, 1H); LC-MS: M+1=207;

1. temperaturecooled with an ice bath
2. customthe reaction's internal temperature below 5° C
3. temperatureThe reaction was cooled
4. customevaporated to dryness
5. extractionextraction with DCM 2×
6. washThe combined DCM layers were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated to dryness
10. customThe residue was chromatographed through a 80 g ISCO Redi-sep column
11. washeluted with solvent system of 5%(10% NH4OH in MeOH)/DCM

ORD record

ord-4f3507b93987470a97bb58bbfb7a13f0

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056859B2