Chloroiodomethane → Tert-butyl 4-(2-chloroacetyl)piperidine-1-carboxylate

HRID 2189499Notes

Reaction equation

HRID 2189499 reaction equation
[N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][CH:4]([C:7]([O:9]C)=O)[CH2:3][CH2:2]1.[Cl:18][CH2:19]I.C[Li]>C1COCC1>[Cl:18][CH2:19][C:7]([CH:4]1[CH2:3][CH2:2][N:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5]1)=[O:9]

Participants

5

Reactant 3

HCID 11644ChloroiodomethaneHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 178418348HCID 178418348, compound

Product 1

HCID 24229336Tert-butyl 4-(2-chloroacetyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (3.6 g, 14.9 mmol) in THF (100 mL) was cooled to −78° C. under nitrogen and then charged with neat chloroiodomethane (1.8 mL, 24.7 mmol). A solution of methyllithium (16.5 mL, 1.5 M in Et2O) was added dropwise. The reaction was stirred for 60 min at −78° C. and then quenched with half-saturated NH4Cl. After warming to room temperature, the mixture was extracted twice with EtOAc. The organic phases were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo to yield impure tert-butyl 4-(2-chloroacetyl)piperidine-1-carboxylate as a dark oil. Key non-solvent resonances in 1H-NMR (400 MHz, d6-DMSO) δ=4.68 (s, 2H), 4.1-3.8 (m, 4H), 2.75 (m, 1H), 1.8 (m, 1H), 1.7-1.5 (m, 2H), 1.4 (s, 9H), 1.4-1.2 (m, 2H).

Workup

  1. customquenched with half-saturated NH4Cl
  2. temperatureAfter warming to room temperature
  3. extractionthe mixture was extracted twice with EtOAc
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-01840b85a4a341ad97feb260c536e1cf
Source dataset
uspto-grants-2012_12
Patent number
US08324251B2

Reaction notes

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