Sodium Iodide → tert-Butyl 4-(acetylthio)piperidine-1-carboxylate

HRID 553603Notes

Reaction equation

HRID 553603 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](Br)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([O-:18])(=[S:17])[CH3:16].[K+].[Na+].[I-]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:17][C:15](=[O:18])[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 15541517tert-Butyl 4-bromopiperidine-1-carboxylateHCID 23670855Potassium ethanethioate

Product 1

HCID 22494773tert-Butyl 4-(acetylthio)piperidine-1-carboxylateYield 173,821.906%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 6.9 g (0.02 mol) of 4-bromo-piperidine-1-carboxylic acid tert-butyl ester in DMF (18 mL) are added 5.25 g (0.012 mmol) potassium thioacetate, followed by a catalytic amount of NaI (0.35 g, 10 mol %) at room temperature. After complete addition, the reaction is heated to 50° C. for 20 h. The reaction mixture is partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer is dried over Na2SO4, filtered and the solvent is removed under reduced pressure to afford 5.41 g of 4-acetylsulfanyl-piperidine-1-carboxylic acid tert-butyl ester as a brown oil. Yield: 81%; ES-MS: m/z 245 [M+H—CH3], 160 [M+H—C5H9O2]; 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 1.37-1.64 (11H, m), 1.78-1.99 (2H, m), 2.25-2.35 (3H, m), 3.06 (2H, ddd, J=13.63, 10.43, 3.05 Hz), 3.61 (1H, tt, J=10.28, 4.04 Hz), 3.76-3.96 (2H, m)

Workup

  1. additionAfter complete addition
  2. customThe reaction mixture is partitioned between ethyl acetate (100 mL) and water (100 mL)
  3. dry with materialThe organic layer is dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-d33261d895914335878cbb45d6400ed4
Source dataset
uspto-grants-2011_11
Patent number
US08048899B2

Reaction notes

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