Ethyl 4-piperidinecarboxylate → tert-Butyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate

HRID 1777292Notes

Reaction equation

HRID 1777292 reaction equation
CS(O[CH:6]1[CH2:9][C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]2)[CH2:7]1)(=O)=O.COC1(C(=O)NC2(C)CCC2)CCN(C2CC3N(C(OCC)=O)C(CC3)C2)CC1.[NH:50]1[CH2:60][CH2:59][CH:53]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[CH2:52][CH2:51]1>>[CH2:57]([O:56][C:54]([CH:53]1[CH2:59][CH2:60][N:50]([CH:6]2[CH2:9][C:8]3([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]3)[CH2:7]2)[CH2:51][CH2:52]1)=[O:55])[CH3:58]

Participants

4

Reactant 3

HCID 70770Ethyl 4-piperidinecarboxylateHCID 73438472Ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylateHCID 86660639tert-Butyl 2-[(methylsulfonyl)oxy]-6-azaspiro[3.4]octane-6-carboxylate

Product 1

HCID 90089413tert-Butyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylateYield 12.5%

Procedure

tert-Butyl 2-[(methylsulfonyl)oxy]-6-azaspiro[3.4]octane-6-carboxylate isomer 1 (1.79 g, 5.73 mmol) and ethyl isonipecotate (4.49 g, 28.62 mmol) were heated together to 65° C. for 5 days. The reaction mixture was reduced in volume in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 100 g, 40-63 μm, 60 A, 50 mL per min, gradient 1% to 4.5% MeOH in DCM]) to give tert-butyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.264 g, 12.5%) as a yellow oil.

Workup

  1. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 100 g, 40-63 μm, 60 A, 50 mL per min, gradient 1% to 4.5% MeOH in DCM])

Sources & evidence

ORD record
ord-5c56a3f668c04c4fa4585016f0ee0ed0
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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