Diisopropylethylamine → Benzamide

HRID 2199866Notes

Reaction equation

HRID 2199866 reaction equation
O1CCN(C[CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH2:9])CC1.C([O:23]C1(OC)C=CC(C(O)=O)=CC1OC)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:8]([NH2:9])(=[O:23])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 28144622-(Morpholin-4-yl)-1-phenylethan-1-amineHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 1176270654-Benzyloxy-3,4-dimethoxybenzoic acid

Product 1

HCID 2331Benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-morpholino-1-phenylethanamine represented by Formula 113 (516.3 mg, 2.50 mmol, purchased from Enamine Co.) was slowly added to 4-benzyloxy-3,4-dimethoxybenzoic acid represented by Formula 89 (793.75 mg, 2.75 mmol) prepared in Preparative Example 1 and diisopropylethylamine (1.75 mL, 10.01 mmol) in DMF (12 mL) at room temperature. After cooling the reaction mixture to 0° C. and adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 1.05 g, 2.75 mmol) thereto, the mixture was agitated at room temperature for 24 hours. The reaction solvent was removed under reduced pressure and chloroform (25 mL) was added to the remaining concentrate to prepare a solution. The solution was washed with a potassium carbonate solution, followed by separation to form an organic layer. After drying the organic layer with sodium sulfate (Na2SO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (ethyl acetate/hexane/triethylamine, 2:1:0.1, v/v/v) using silica gel (SiO2), resulting in a benzamide compound represented by Formula 20 as a desired product (VVZ-021; 355.2 mg, 30% yield).

Workup

  1. customThe reaction solvent was removed under reduced pressure and chloroform (25 mL)
  2. additionwas added to the
  3. concentrationremaining concentrate
  4. customto prepare a solution
  5. washThe solution was washed with a potassium carbonate solution
  6. customfollowed by separation
  7. customto form an organic layer
  8. dry with materialAfter drying the organic layer with sodium sulfate (Na2SO4)
  9. customthe solvent was removed again under reduced pressure
  10. concentrationThe obtained vacuum-concentrated mixture
  11. customwas subjected to separation and purification through column chromatography (ethyl acetate/hexane/triethylamine, 2:1:0.1, v/v/v)

Sources & evidence

ORD record
ord-cee7b7e0cabc434d923d17e9b5d40077
Source dataset
uspto-grants-2016_06
Patent number
US09359346B2

Reaction notes

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