Iodoethane → ethyl 6-{[(3R)-1-benzyl-3-piperidinyl]amino}-5-chloronicotinate

Temperature

45 °C

To a solution of 5,6-dichloronicotinic acid (7.0 g, 35 mmol) in DMF were added iodoethane (6.0 g, 38.5 mmol) and K2CO3 (5.8 g, 42 mmol) at ambient temperature and the mixture was stirred at 45° C. for 5 hrs. To the reaction mixture were added (3R)-1-benzyl-3-piperidinamine dihydrochloride (10.1 g, 38.5 mmol) and K2CO3 (16.9 g, 122 mmol) and the reaction mixture was stirred at 90° C. for 18 hrs. The reaction mixture was evaporated in vacuo and the residue was partitioned between water and EtOAc. The organic layer was separated, washed water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (EtOAc-hexane/1-4˜1-3) to give ethyl 6-{[(3R)-1-benzyl-3-piperidinyl]amino}-5-chloronicotinate (6.75 g, 52%) as a powder.

1. stirringthe reaction mixture was stirred at 90° C. for 18 hrs
2. customThe reaction mixture was evaporated in vacuo
3. customthe residue was partitioned between water and EtOAc
4. customThe organic layer was separated
5. washwashed water and brine
6. dry with materialdried over magnesium sulfate
7. customevaporated in vacuo
8. customThe residue was purified by silica gel column chromatography (EtOAc-hexane/1-4˜1-3)

ORD record

ord-a483510810994e1fbb9c23a716e35eeb

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07465731B2