Phenacyl bromide → tert-Butyl 4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxylate

HRID 1695881Notes

Reaction equation

HRID 1695881 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[NH2:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.CCN(C(C)C)C(C)C.[O-:34][C:35]#[N:36].[Na+]>C(Cl)Cl.O.C(O)(=O)C>[O:34]=[C:35]1[N:11]([CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]2)[CH:2]=[C:3]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[NH:36]1

Participants

8

Reactant 4

HCID 6259Phenacyl bromideHCID 81531DiisopropylethylamineHCID 517096Sodium CyanateHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 11653081tert-Butyl 4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyl 4-(1,2-dihydro-2-oxo-5-phenylimidazol-3-yl)piperidine-1-carboxylate was synthesised as described in J. Med. Chem., 2005, 48, 5921. A solution of 2-bromo-1-phenylethanone (5 g, 25 mmol) in DCM (10 ml) was added dropwise to a stirred solution of tert-butyl 4-aminopiperidine-1-carboxylate (6 g, 30 mmol) and DIPEA (9.84 ml, 57.5 ml) in DCM (50 ml) over 1 hour, the reaction mixture was then stirred at room temperature for 16 hours. Sodium cyanate (3.41 g, 52.5 mmol) was added, the reaction mixture was then cooled to 0° C., the pH was brought to pH 4 with acetic acid and the reaction mixtures was stirred from 0° C. to RT over 16 hours. The reaction mixture was poured into water and extracted with DCM (3×). Organics combined, washed with water (3×), brine, dried (MgSO4) and evaporated to dryness. The residue was triturated with ether, filtered and the solid was washed with ether to give a pale yellow solid (4.04 g, 47%). LC/MS (10% to 99%): M/Z (M+H)+ (obs)=344; tR=3.01.

Workup

  1. temperaturethe reaction mixture was then cooled to 0° C.
  2. customthe reaction mixtures
  3. stirringwas stirred from 0° C. to RT over 16 hours
  4. extractionextracted with DCM (3×)
  5. washwashed with water (3×), brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. customThe residue was triturated with ether
  9. filtrationfiltered
  10. washthe solid was washed with ether

Sources & evidence

ORD record
ord-2628923f62be4fd29cb88f21bec66857
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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