Ethyl Acetate → HCID 67104131, compound

HRID 1984780Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[CH2:19][O:20][C:21]([CH3:23])=[O:22]>CS(C)=O.C1(C)C=CC=CC=1>[CH3:19][O:20][C:21]([C:23]1[CH:11]=[CH:10][C:9]([N:15]2[CH2:16][CH2:17][C:10]3([CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:12][CH2:11]3)[CH2:13][CH2:14]2)=[N:8][CH:6]=1)=[O:22]

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of methyl 6-chloronicontinate (200 mg, 1.16 mmol) in DMSO/PhMe (2 mL of a 1:1 solution) was added t-butyl-2,8-diazaspiro[4.5]decane-2-carboxylate (700 mg, 2.91 mmol). The reaction mixture was heated at 85° C. for 6 hours and then diluted with EtOAc (10 mL). The organic layer was washed with NaHCO3 (1×5 mL) and brine (1×5 mL), dried over Na2SO4, and then concentrated. The crude residue was purified by reverse-phase flash chromatography (10-100% MeCN/H2O with 0.05% TFA) to give t-butyl 8-[5-(methoxycarbonyl)pyridin-2-yl]-2,8-diazaspiro[4.5]decane-2-carboxylate: MS (ESI+): cal'd [M+H]+ 376.2, obs'd 376.2. This intermediate was then treated with TFA (3 mL) in CH2Cl2 (6 mL). The reaction mixture was concentrated after 30 minutes of stirring at room temperature and the crude residue was purified by reverse-phase flash chromatography (10-75% MeCN/H2O with 0.05% TFA) to give the methyl 6-(2,8-diazaspiro[4.5]dec-8-yl)nicotinate: MS (ESI+): cal'd [M+H]+ 276.2, obs'd 276.2.

Workup

washThe organic layer was washed with NaHCO3 (1×5 mL) and brine (1×5 mL)
dry with materialdried over Na2SO4
concentrationconcentrated
customThe crude residue was purified by reverse-phase flash chromatography (10-100% MeCN/H2O with 0.05% TFA)

Sources & evidence

ORD record: ord-65abf01ab72b4f42b37524c29c44ac2d
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07544695B2

Reaction notes

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