Ethyl Acetate → HCID 178451791, compound

HRID 419708Notes

Reaction equation

HRID 419708 reaction equation
C(O)(=O)C.[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([CH:18]([NH2:20])[NH2:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=1)=O.C(OCC)(=O)C>CN(C=O)C>[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[NH:19][CH:28]=[C:29]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=3)[N:20]=2)[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 387382-Bromo-3'-chloroacetophenoneHCID 66649968HCID 66649968, compound

Product 1

HCID 178451791HCID 178451791, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Suspend 4-Diaminomethyl-piperidine-1-carboxylic acid tert-butyl ester acetic acid salt (685 mg; 1.00 equiv; 2.38 mmoles) in dimethylformamide (10 mL; 129.33 mmoles) and add powdered potassium carbonate (1400 mg; 10.13 mmoles). Stir 10 minutes at room temperature then add 2-Bromo-1-(3-chloro-phenyl)-ethanone (1400 mg; 6.00 mmoles) dissolved in 4 mL DMF dropwise to the amidine at room temperature. After 3 h, dilute the reaction with ethyl acetate and wash with 50% aq. sodium bicarbonate. Dry the organic layer over sodium sulfate, filter and concentrate to a crude oil. Purify using ISCO chromatography over a biotage 40M column, eluting with a gradient of DCM to 6% MeOH/DCM. Concentrate the appropriate fractions to give a 20% yield of 4-[4-(3-Chloro-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester. MS (ES): m/z=262.0 [M+H].

Workup

  1. waitAfter 3 h
  2. additiondilute
  3. washwash with 50% aq. sodium bicarbonate
  4. dry with materialDry the organic layer over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate to a crude oil
  7. customPurify
  8. washeluting with a gradient of DCM to 6% MeOH/DCM
  9. concentrationConcentrate the appropriate fractions

Sources & evidence

ORD record
ord-a7791e634a624db9bceaf391e0f58fbf
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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