Methanol → Tert-butyl 4-(5-bromo-4-methylthiophen-2-yl)piperidine-1-carboxylate

HRID 446731Notes

Reaction equation

HRID 446731 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[S:5][CH:6]=1.CO.[Br:22]N1C(=O)CCC1=O>[Pd].C(OCC)(=O)C>[Br:22][C:6]1[S:5][C:4]([CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]2)=[CH:3][C:2]=1[CH3:1]

Participants

6

Reactant 3

HCID 887MethanolHCID 67184N-bromobutanimideHCID 67027249HCID 67027249, compound

Product 1

HCID 67027226Tert-butyl 4-(5-bromo-4-methylthiophen-2-yl)piperidine-1-carboxylateYield 58.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To Compound 1062 (1.67 g, 5.98 mmol) in a solution of methanol and ethyl acetate (40 mL, 1:1) was added palladium on carbon (1 g, 10%, Degussa type). The reaction was shaken under hydrogen atmosphere at 45 psi on a Parr apparatus for 1 hour, filtered through diatomaceous earth, and concentrated under reduced pressure. The resulting material was dissolved in acetonitrile (30 mL) and treated with N-bromosuccinimide (1.14 g, 6.4 mmol). The reaction mixture was stirred for 30 minutes at room temperature and quenched with a saturated solution of sodium sulfite. The crude product was extracted with EtOAc (2×30 mL) and the combined organics were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified via silica gel chromatography to provide 1.26 g of tert-butyl 4-(5-bromo-4-methylthiophen-2-yl)piperidine-1-carboxylate Compound 1063) as a pale yellow solid; 1H NMR (300 MHz, CDCl3): δ 6.42 (s, H), 4.20-4.01 (m, 2H), 2.77-2.68 (m, 3H), 2.05 (s, 3H), 1.84 (d, J=12.3 Hz, 2H) and 1.50-1.39 (m, 11H).

Workup

  1. filtrationfiltered through diatomaceous earth
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe resulting material was dissolved in acetonitrile (30 mL)
  4. stirringThe reaction mixture was stirred for 30 minutes at room temperature
  5. customquenched with a saturated solution of sodium sulfite
  6. extractionThe crude product was extracted with EtOAc (2×30 mL)
  7. dry with materialthe combined organics were dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-9a796a27ef984dae88a44a9833599859
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

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