Toluene → HCID 59729986, compound

HRID 228259Notes

Reaction equation

HRID 228259 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4].Cl[C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][N:21]=1.C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>CN(C=O)C>[F:18][C:2]([F:1])([F:17])[C:3]([N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([O:16][C:20]3[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][N:21]=3)[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 804566-ChloronicotinamideHCID 59730230HCID 59730230, compound

Product 1

HCID 59729986HCID 59729986, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Add 2,2,2-trifluoro-1-(7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)ethanone (0.750 g, 2.89 mmol), 6-chloronicotinamide (0.377 g, 2.41 mmol) and K2CO3 (0.833 g, 6.03 mmol) to a round bottom equipped with a Dean-Stark trap. Add toluene (6 mL) and DMF (18 mL). Heat at reflux for two hours. Cool the reaction mixture to 100° C. and stir overnight. Remove the toluene and DMF as an azeotrope with xylenes. Suspend the solid in 5% methanol/ethyl acetate (100 mL) and filter. Wash the filter cake with ethyl acetate. Concentrate the filtrate, then purify by flash chromatography, eluting with 40% ethyl acetate in dichloromethane to give the title compound (0.312 g, 34.0%):

Workup

  1. custombottom equipped with a Dean-Stark trap
  2. temperatureHeat
  3. temperatureat reflux for two hours
  4. customRemove the toluene and DMF as an azeotrope with xylenes
  5. filtrationfilter
  6. washWash the filter cake with ethyl acetate
  7. concentrationConcentrate the filtrate
  8. custompurify by flash chromatography
  9. washeluting with 40% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-31dfc172a3e3451a818c74ecceebc187
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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