Dimethyl Sulfide → Ethyl 1-(4-chlorophenylsulfonyl)-6-ethyl-4-oxopiperidine-2-carboxylate

HRID 15743

Reaction equation

HRID 15743 reaction equation
S(C)C.[CH2:4]([Mg]Br)[CH3:5].[B-](F)(F)(F)[O+](C)C.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]2[CH:30]=[CH:29][C:28](=[O:31])[CH2:27][CH:26]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])(=[O:24])=[O:23])=[CH:18][CH:17]=1>C1COCC1>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]2[CH:30]([CH2:4][CH3:5])[CH2:29][C:28](=[O:31])[CH2:27][CH:26]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])(=[O:23])=[O:24])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 59342383Ethyl 1-(4-chlorophenylsulfonyl)-4-oxo-1,2,3,4-tetrahydropyridine-2-carboxylateHCID 178418443HCID 178418443, compoundHCID 178494437HCID 178494437, compound

Product 1

HCID 59342392Ethyl 1-(4-chlorophenylsulfonyl)-6-ethyl-4-oxopiperidine-2-carboxylateYield 88.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

CuBr2.SMe2 (19.13 g, 93.1 mmol) was placed into a flame-dried flask along with THF (250 ml). The mixture was cooled to −78° C. and ethylmagnesium bromide (31 ml, 3.0 M in ether, 93.1 mmol) was added slowly. The reaction was stirred for 45 minutes under nitrogen. Boron trifluoride dimethyl etherate was added (11.7 ml, 93,1 mmol) and the mixture stirred for 5 minutes. Ethyl 1-(4-chlorophenylsulfonyl)-4-oxo-1,2,3,4-tetrahydropyridine-2-carboxylate (103; 8.0 g, 23.3 mmol) was added via syringe pump over a 2 hour period while maintaining −78° C. bath temperature. The reaction was stirred for 4 hours and quenched with a 1:1 solution of 2% NH4Cl/NH4OH. An equal amount of EtOAc and water was added and the mixture was filtered to remove solids. The layers were separated and the aqueous layer was extracted with two more portions of EtOAc. The organic layers were combined and dried over Na2SO4 and concentrated to yield a colorless oil (7.74 g). The material was purified by column chromatography using EtOAc/hexanes gradients to yield 5.84 g (67%) of a mixture of cis/trans (4:96) isomers.

Workup

  1. stirringthe mixture stirred for 5 minutes
  2. temperaturewhile maintaining −78° C. bath temperature
  3. stirringThe reaction was stirred for 4 hours
  4. customquenched with a 1:1 solution of 2% NH4Cl/NH4OH
  5. additionAn equal amount of EtOAc and water was added
  6. filtrationthe mixture was filtered
  7. customto remove solids
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with two more portions of EtOAc
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b5fe59881ddc4847a56c92490d66c453
Source dataset
uspto-grants-2010_06
Patent number
US07732609B2

Linked notes

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