Trifluoroacetic acid → 1-(6-azaspiro[3.4]oct-2-yl)-N-(1-methylcyclobutyl)piperidine-4-carboxamide trifluoroacetate

HRID 1777291Notes

Reaction equation

HRID 1777291 reaction equation
[CH3:1][C:2]1([NH:6][C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:18][C:17]4([CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]4)[CH2:16]3)[CH2:11][CH2:10]2)=[O:8])[CH2:5][CH2:4][CH2:3]1.[C:30]([OH:36])([C:32]([F:35])([F:34])[F:33])=[O:31]>C(Cl)Cl>[F:33][C:32]([F:35])([F:34])[C:30]([OH:36])=[O:31].[CH2:18]1[C:17]2([CH2:22][CH2:21][NH:20][CH2:19]2)[CH2:16][CH:15]1[N:12]1[CH2:11][CH2:10][CH:9]([C:7]([NH:6][C:2]2([CH3:1])[CH2:5][CH2:4][CH2:3]2)=[O:8])[CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90089500Tert-butyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate

Product 1

HCID 900826771-(6-azaspiro[3.4]oct-2-yl)-N-(1-methylcyclobutyl)piperidine-4-carboxamide trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

LCMS (Method A): m/z 406 (M+H)+ (ES+), at 1.81 min, UV inactive tert-Butyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.627 g, 1.55 mmol) was dissolved in DCM (8 mL) and TFA (2 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-(1-methylcyclobutyl)piperidine-4-carboxamide trifluoroacetate as a dark yellow oil which was used directly without further purification. The residue was dissolved in DCM (10 mL) and NEt3 (0.49 g, 0.65 mL, 4.64 mmol) and ethyl chloroformate (0.25 mg, 0.18 mL, 0.57 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-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.04 g, 13%) as a yellow gum as a mixture of diastereomers.

Workup

  1. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-cd52ea22649a4a17b66173f122429311
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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