Hydrochloric Acid → HCID 58293743, compound

HRID 446728Notes

Reaction equation

HRID 446728 reaction equation
CC[Mg+].[Br-].Br[C:6]1[S:7][CH:8]=[CH:9][C:10]=1[CH3:11].[O:12]=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.Cl>C1COCC1.CCOC(C)=O>[OH:12][C:13]1([C:6]2[S:7][CH:8]=[CH:9][C:10]=2[CH3:11])[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 843142-Bromo-3-methylthiopheneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178461630HCID 178461630, compound

Product 1

HCID 58293743HCID 58293743, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of EtMgBr (300 mL of 1.0M, 300 mmol) in THF (400 mL) at RT was added 2-bromo-3-methylthiophene (48.28 g, 272.7 mmol) dropwise. The mixture was stirred at RT for 72 hours. To the reaction mixture was added a solution of tert-butyl 4-oxopiperidine-1-carboxylate (54.33 g, 272.7 mmol) in THF at RT. The reaction was stirred for 3 hours and 2 N HCl was added to quench the reaction. The mixture was extracted with EtOAc and the combined organics washed with water, satd' NaHCO3 solution, and dried over MgSO4. Removal of the volatiles in vacuo gave a gummy product, to which was added EtOAc. After shaking for 10 min a white precipitate appeared, which was collected by filtration and washed with EtOAc. The filtrate was evaporated again and the precipitation step repeated to obtain additional product, which was combined with the solid previously collected to yield tert-Butyl 4-hydroxy-4-(3-methylthiophen-2-yl)piperidine-1-carboxylate (Compound 1052, 58 g, 71.5% yield; 1H NMR (300 MHz, DMSO-d6): δ 7.17 (d, J=5.0 Hz, 1H), 6.79 (d, J=5.1 Hz, 1H), 5.47 (s, 1H), 3.82 (brd, 2H), 3.09 (brs, 2H), 2.26 (s, 3H), 1.84-1.79 (m, 4H) and 1.41 (s, 9H).

Workup

  1. stirringThe reaction was stirred for 3 hours
  2. customto quench
  3. customthe reaction
  4. extractionThe mixture was extracted with EtOAc
  5. washthe combined organics washed with water
  6. dry with materialdried over MgSO4
  7. customRemoval of the volatiles in vacuo
  8. customgave a gummy product
  9. stirringAfter shaking for 10 min a white precipitate
  10. filtrationwhich was collected by filtration
  11. washwashed with EtOAc
  12. customThe filtrate was evaporated again
  13. customthe precipitation step
  14. customto obtain additional product, which
  15. custompreviously collected

Sources & evidence

ORD record
ord-046ea2beaba743e8aff8860702989b9b
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

Loading…