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

HRID 1777293Notes

Reaction equation

HRID 1777293 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:15][C:14]3([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23](C)(C)[CH3:24])=[O:21])[CH2:16]3)[CH2:13]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Cl.O1CCOCC1.CCN(CC)CC.ClC(OCC)=O>C(Cl)Cl>[CH2:1]([O:3][C:4]([CH:6]1[CH2:7][CH2:8][N:9]([CH:12]2[CH2:15][C:14]3([CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16]3)[CH2:13]2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 204431481,4-Dioxane hydrochlorideHCID 90089413tert-Butyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate

Product 1

HCID 90079706Ethyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

LCMS (Method A): m/z 367 (M+H)+ (ES+), at 1.97 min, UV inactive. tert-Butyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.080 g, 0.22 mmol) was stirred in DCM (10 mL) at rt and treated with 4 M HCl/dioxane (1 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was conc. in vacuo to give a yellow solid that was used directly without further purification. The residue was dissolved in DCM (10 mL) and NEt3 (0.066 g, 0.1 mL, 0.66 mmol) and ethyl chloroformate (0.036 g, 0.03 mL, 0.32 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 8% MeOH in DCM]) to give ethyl 2-[4-(ethoxycarbonyl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate (0.069 g, 93%) as an amber oil.

Workup

  1. customto give a yellow solid that
  2. customwas used directly without further purification
  3. dissolutionThe residue was dissolved in DCM (10 mL)
  4. stirringthe reaction mixture was stirred at rt overnight under nitrogen
  5. customThe solvents were removed in vacuo
  6. customthe residue was partitioned between DCM and sat. NaHCO3 sol., organic layer
  7. washwashed with sat. NaCl sol.
  8. dry with materialdried over MgSO4
  9. customThe 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 8% MeOH in DCM])

Sources & evidence

ORD record
ord-2419a25fb15e4b22b413db73cddc7182
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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