Trifluoroacetic acid → HCID 90079530, compound

HRID 1777296Notes

Reaction equation

HRID 1777296 reaction equation
[F:1][C:2]1([C:23]([O:25]C)=[O:24])[CH2:7][CH2:6][N:5]([CH:8]2[CH2:11][C:10]3([CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]3)[CH2:9]2)[CH2:4][CH2:3]1.[C:27]([OH:33])([C:29]([F:32])([F:31])[F:30])=[O:28]>C(Cl)Cl>[F:30][C:29]([F:32])([F:31])[C:27]([OH:33])=[O:28].[CH2:11]1[C:10]2([CH2:15][CH2:14][NH:13][CH2:12]2)[CH2:9][CH:8]1[N:5]1[CH2:6][CH2:7][C:2]([F:1])([C:23]([O:25][CH2:27][CH3:29])=[O:24])[CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90089433HCID 90089433, compound

Product 1

HCID 90079530HCID 90079530, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-[4-fluoro-4-(methoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.300 g, 0.81 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 ethyl 1-(6-azaspiro[3.4]oct-2-yl)-4-fluoropiperidine-4-carboxylate trifluoroacetate, as a dark yellow oil which was used directly without further purification. The residue was dissolved in DCM (8 mL) at rt. NEt3 (0.246 g, 0.34 mL, 2.43 mmol) and ethyl chloroformate (0.176 g, 0.16 mL, 1.62 mmol) were added and the reaction mixture was stirred at rt overnight under nitrogen. The reaction mixture 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-fluoro-4-(methoxycarbonyl) piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.440 g, 158% impure) as a pale yellow oil.

Workup

  1. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-8863c5a7a4454883a4d41677f8e0d9e9
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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