4-Methylmorpholine → 3-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide

HRID 1402490Notes

Reaction equation

HRID 1402490 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[F:18])[C:12]([OH:14])=O)[CH:5]=[CH:4][N:3]=1.[F:19][C:20]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:21]=1[NH2:22].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[F:18])[C:12]([NH:22][C:21]2[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:20]=2[F:19])=[O:14])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2629702-Fluoro-5-methylanilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581677923-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid

Product 1

HCID 866515583-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(2-Chloropyridin-4-yloxy)-4-fluorobenzoic acid (2.22 g, 8.29 mmol), 2-fluoro-5-methylaniline (1.56 g, 12.4 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 3.78 g, 9.95 mmol) and N-methylmorpholine (2.00 mL, 18.2 mmol) in dimethylformamide (22 mL) was heated at 90° C. for 2 h. The solvent was evaporated in vacuo at 50° C. To the residue was added water resulting in a thick oil. The water was decanted and the oil dissolved in EtOAc then extracted twice with water, 1M hydrochloric acid and brine. The organic layer was dried (MgSO4), filtered and evaporated to crude 6 (3.37 g). Trituration with dichloromethane (25 mL) gave 3-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide as white solid. Yield: 1.788 g, 58%.

Workup

  1. customThe solvent was evaporated in vacuo at 50° C
  2. additionTo the residue was added water resulting in a thick oil
  3. customThe water was decanted
  4. dissolutionthe oil dissolved in EtOAc
  5. extractionthen extracted twice with water, 1M hydrochloric acid and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated to crude 6 (3.37 g)

Sources & evidence

ORD record
ord-360e29a183d34955a0d194aa4741e0b8
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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