Ethylamine → 4-[Ethyl-(4-methoxy-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2354046Notes

Reaction equation

HRID 2354046 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([NH2:17])[CH3:16].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C1COCC1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:17]([CH2:15][CH3:16])[S:26]([C:23]2[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=2)(=[O:28])=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6341EthylamineHCID 74014-Methoxybenzenesulfonyl chlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 686888764-[Ethyl-(4-methoxy-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of commercially available 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5.58 g, 28 mmol) and ethylamine (2 M in THF, 50 mL, 100 mmol) in THF (100 mL) is stirred at r.t. for 2 h. NaBHAc3 (8.9 g, 42 mmol) is added and the mixture is stirred for 15 h. The mixture is quenched with 1 M aq. NaOH (100 mL) and stirred at r.t. for 6 h. The mixture is extracted with CH2Cl2 (150 mL, then 4×50 mL) and the combined organic extracts are washed with 1 M aq. NaOH (30 mL). The organic phase is dried (Na2SO4), filtered and evaporated. The residue is dissolved in CH2Cl2 (100 mL) and TEA (3 g, 30 mmol) and, subsequently, a solution of 4-methoxy-benzenesulfonylchloride (6.38 g, 30.9 mmol) in CH2Cl2 (10 mL) are added at 0° C. The mixture is warmed to r.t. during 15 h and quenched with 1 M aq. NaOH (30 mL). The phases are separated and the organic phase is washed with 1 M aq. NaOH (30 mL), 1 M aq. KHSO4 (2×30 mL) and sat. aq. NaCl (30 mL). The organic phase is dried (Na2SO4), filtered and evaporated. The residue is purified by FC (SiO2, EtOAc-heptane) to provide the title compound.

Workup

  1. additionNaBHAc3 (8.9 g, 42 mmol) is added
  2. stirringthe mixture is stirred for 15 h
  3. customThe mixture is quenched with 1 M aq. NaOH (100 mL)
  4. stirringstirred at r.t. for 6 h
  5. extractionThe mixture is extracted with CH2Cl2 (150 mL
  6. wash4×50 mL) and the combined organic extracts are washed with 1 M aq. NaOH (30 mL)
  7. dry with materialThe organic phase is dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe residue is dissolved in CH2Cl2 (100 mL)
  11. temperatureThe mixture is warmed to r.t. during 15 h
  12. customquenched with 1 M aq. NaOH (30 mL)
  13. customThe phases are separated
  14. washthe organic phase is washed with 1 M aq. NaOH (30 mL), 1 M aq. KHSO4 (2×30 mL) and sat. aq. NaCl (30 mL)
  15. dry with materialThe organic phase is dried (Na2SO4)
  16. filtrationfiltered
  17. customevaporated
  18. customThe residue is purified by FC (SiO2, EtOAc-heptane)

Sources & evidence

ORD record
ord-079def1a484e4ee185e0a7822d399f61
Source dataset
uspto-grants-2010_07
Patent number
US07750161B2

Reaction notes

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