Tert-Butylamine → methyl 2-amino-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxylate

Temperature

0 °C

To a solution of methyl 6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxylate 1-oxide (700 mg, 3.6 mmol) in CF3-toluene (20 mL) and CHCl3 (20 mL) was added tert-butylamine (3.8 mL, 36 mmol). The solution was cooled to 0° C. in an ice bath. To the solution was added p-toluenesulfonic anhydride (3.5 g, 10.9 mmol) in small portions until all SM was consumed according to LC-MS. The volatiles were removed under reduced pressure, and the residue was redissolved in TFA (20 mL). The dark solution was heated to 70° C. for 2 hours. LC showed mostly product, with a little bit SM remaining. The reaction was stopped at that point. TFA was removed on a rotavapor, and the residue was taken up in saturated sodium carbonate, extracted three times with IPA-CHCl3 (1:3, 50 mL each). The extractions were combined, dried over sodium sulfate, adsorbed onto silica gel, and purified by MPLC (DCM:MeOH with 10% aq NH4OH). After removal of solvent was collected as the desired methyl 2-amino-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxylate. LC-MS (IE, m/z): 193 [M+1]+;

1. customwas consumed
2. customThe volatiles were removed under reduced pressure
3. dissolutionthe residue was redissolved in TFA (20 mL)
4. temperatureThe dark solution was heated to 70° C. for 2 hours
5. customTFA was removed on a rotavapor
6. extractionextracted three times with IPA-CHCl3 (1:3, 50 mL each)
7. extractionThe extractions
8. dry with materialdried over sodium sulfate
9. custompurified by MPLC (DCM:MeOH with 10% aq NH4OH)
10. customAfter removal of solvent
11. customwas collected as the desired methyl 2-amino-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxylate

ORD record

ord-13284d429c5b464794169cf8abfbe319

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056859B2