Sodium Methoxide → 4-[1-Methyl-1-(5-trifluoromethyl-pyridin-2-ylcarbamoyl)-ethylsulfanylmethyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 73241Notes

Reaction equation

HRID 73241 reaction equation
[CH3:1][C:2]([S:17][C:18](=O)[CH3:19])([C:4](=[O:16])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=1)[CH3:3].[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32]C(CBr)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C[O-].[Na+]>C(O)C>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:1]([C:2]([S:17][CH2:18][CH3:19])([CH3:3])[C:4](=[O:16])[NH:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 59703968thioacetic acid S-[1-methyl-1-(5-trifluoromethyl-pyridin-2-ylcarbamoyl)-ethyl]ester

Product 1

HCID 670972564-[1-Methyl-1-(5-trifluoromethyl-pyridin-2-ylcarbamoyl)-ethylsulfanylmethyl]-piperidine-1-carboxylic acid tert-butyl esterYield 124.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 200 mg (0.654 mmol) of thioacetic acid S-[1-methyl-1-(5-trifluoromethyl-pyridin-2-ylcarbamoyl)-ethyl]ester (synthesized according to Method F, step 1) in ethanol (2 mL) were added 363 mg (1.31 mmol) of 4-bromomethyl-piperidine-1-carboxylic acid tert-butyl ester and 141 mg (2.61 mmol) of sodium methoxide at room temperature. The reaction was heated to 130° C. for 0.5 h within a microwave (CEM Discover). The reaction mixture was concentrated under reduced pressure. The residue was dissolved in DCM (4 mL) and washed with saturated aqueous NaHCO3 solution (5 mL). The organic phase was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure to yield 375 mg of 4-[1-methyl-1-(5-trifluoromethyl-pyridin-2-ylcarbamoyl)-ethylsulfanylmethyl]-piperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in DCM (4 mL)
  3. washwashed with saturated aqueous NaHCO3 solution (5 mL)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-701c0c7195a14f8ca382f950095509de
Source dataset
uspto-grants-2014_09
Patent number
US08829034B2

Reaction notes

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