Diisopropylethylamine → 4-bromo-2-chloro-5-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234515Notes

Reaction equation

HRID 2234515 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([Cl:12])[CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:37][N:38]1[CH2:43][CH2:42][CH:41]([NH2:44])[CH2:40][CH2:39]1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([NH:44][CH:41]2[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]2)=[O:8])=[C:4]([Cl:12])[CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27362254-Bromo-2-chloro-5-fluorobenzoic acidHCID 27375314-Amino-1-methylpiperidine

Product 1

HCID 686807324-bromo-2-chloro-5-fluoro-N-(1-methyl-4-piperidyl)benzamideYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-bromo-2-chloro-5-fluoro-benzoic acid (Apollo Scientific; 5.0 g, 19.8 mmol) was added to DMF (250 mL), to this was added HBTU (9.8 g, 25.7 mmol), N-methyl-4-aminopiperidine (Fluorochem; 2.5 g, 21.8 mmol) and DIPEA (7.0 mL, 39.5 mmol). The reaction was stirred overnight, evaporated to dryness, quenched with 2.0 N NaOH (100 mL), extracted with DCM (3×100 mL), dried and solvent removed in vacuo. The residue was dissolved in hot acetonitrile, allowed to cool filtered, and the filtrate passed through a SCX column and the residue, after evaporation of product containing fractions, recrystallised from hot acetonitrile to yield the title compound as a white solid (5.0 g, 82%).

Workup

  1. customevaporated to dryness
  2. customquenched with 2.0 N NaOH (100 mL)
  3. extractionextracted with DCM (3×100 mL)
  4. customdried
  5. customsolvent removed in vacuo
  6. dissolutionThe residue was dissolved in hot acetonitrile
  7. temperatureto cool
  8. filtrationfiltered
  9. customthe residue, after evaporation of product
  10. additioncontaining fractions
  11. customrecrystallised from hot acetonitrile

Sources & evidence

ORD record
ord-1948032135f6477d9bd7212da31890f4
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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