Acetamide → HCID 90034137, compound

HRID 56257Notes

Reaction equation

HRID 56257 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:28])[CH2:16][C:17](=O)[CH2:18][O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[C:29]([NH2:32])(=O)[CH3:30].C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1(C)C(C)=CC=CC=1.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4]>[F:1][C:2]1[CH:3]=[C:4]([N:14]2[C:15](=[O:28])[CH:16]=[C:17]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[N:32]=[C:29]2[CH3:30])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 178AcetamideHCID 1140TolueneHCID 25517Ammonium ChlorideHCID 90022866HCID 90022866, compound

Product 1

HCID 90034137HCID 90034137, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
165 °C

Procedure

A mixture of N-(3-fluoro-4-morpholinophenyl)-4-(3-fluorophenoxy)-3-oxobutanamide (510 mg, 1.31 mmol), acetamide (154 mg, 2.61 mmol) and titanium tetraisopropanolate (3.2 mL) in xylene (10 mL) was stirred at 165° C. for 24 h. The mixture was cooled to rt and 60 mL of toluene and 60 mL of saturated NH4Cl aqueous solution were added. The resulting mixture was stirred at rt overnight. The mixture was then filtered and the filtrate was extracted with DCM (20 mL×4). The combined organic phases were washed with brine (30 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as a yellow solid (0.09 g, 17%). The compound was characterized by the following spectroscopic data:

Workup

  1. temperatureThe mixture was cooled to rt
  2. stirringThe resulting mixture was stirred at rt overnight
  3. filtrationThe mixture was then filtered
  4. extractionthe filtrate was extracted with DCM (20 mL×4)
  5. washThe combined organic phases were washed with brine (30 mL×2)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

Sources & evidence

ORD record
ord-7f94b84019aa46418f584cd9e738e261
Source dataset
uspto-grants-2016_09
Patent number
US09434695B2

Reaction notes

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