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

HRID 2376057Notes

Reaction equation

[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].I[CH2:13][CH3:14].C([O-])([O-])=O.[K+].[K+].Cl.Cl.[CH2:23]([N:30]1[CH2:35][CH2:34][CH2:33][C@@H:32]([NH2:36])[CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[CH2:23]([N:30]1[CH2:35][CH2:34][CH2:33][C@@H:32]([NH:36][C:3]2[C:2]([Cl:1])=[CH:10][C:6]([C:7]([O:9][CH2:13][CH3:14])=[O:8])=[CH:5][N:4]=2)[CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

Conditions

Temperature: 45 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-a483510810994e1fbb9c23a716e35eeb
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07465731B2

Reaction notes

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