Trifluoroacetic acid → 1-(6-azaspiro[3.4]oct-2-yl)-N-tert-butylpiperidine-4-carboxamide trifluoroacetate
Reaction equation
C(OC([N:8]1[CH2:28][CH2:27][C:10]2([CH2:13][CH:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20](=[O:26])[NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:16][CH2:15]3)[CH2:11]2)[CH2:9]1)=O)(C)(C)C.[C:29]([OH:35])([C:31]([F:34])([F:33])[F:32])=[O:30]>C(Cl)Cl>[F:32][C:31]([F:34])([F:33])[C:29]([OH:35])=[O:30].[CH2:11]1[C:10]2([CH2:27][CH2:28][NH:8][CH2:9]2)[CH2:13][CH:12]1[N:14]1[CH2:15][CH2:16][CH:17]([C:20]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:26])[CH2:18][CH2:19]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
tert-Butyl-2-[4-(tert-butylcarbamoyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.627 g, 1.55 mmol) was dissolved in DCM (4 mL) and TFA (1 mL) was added. The reaction mixture was stirred at rt overnight under nitrogen, then the solvents were removed in vacuo, to give 1-(6-azaspiro[3.4]oct-2-yl)-N-tert-butylpiperidine-4-carboxamide trifluoroacetate (1:2) as an oil which was used directly without further purification. The residue was dissolved in DCM (8 mL) and NEt3 (0.056 g, 0.08 mL, 0.54 mmol) and ethyl chloroformate (0.024 mg, 0.02 mL, 0.22 mmol) were added and the reaction mixture was stirred at rt overnight under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over MgSO4. The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 10% MeOH in DCM]) to give ethyl 2-[4-(tert-butylcarbamoyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.027 g, 41%) as an off-white solid as a mixture of diastereomers.
Workup
- customthe solvents were removed in vacuo
Sources & evidence
- ORD record
- ord-1045c439ee17418dac930c23c541db8e
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09266857B2
Reaction notes
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