Diisopropylethylamine → 4-amino-N-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamide

HRID 1676535Notes

Reaction equation

HRID 1676535 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][C:12]([F:15])([F:14])[F:13].[NH2:16][CH:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1.C(N(C(C)C)C(C)C)C>CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+]>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:16][CH:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[O:8])=[CH:4][C:3]=1[O:11][C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27359514-amino-3-(trifluoromethoxy)benzoic AcidHCID 27375314-Amino-1-methylpiperidine

Product 1

HCID 580151524-amino-N-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamideYield 95.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 0.5 g (2.3 mmole) of 4-amino-3-trifluoromethoxy-benzoic acid, 0.31 g (2.8 mmole) of 4-amino-1-methyl-piperidine, 1.2 mL (69 mmole) of ethyldiisopropyl amine and 4 mL of dimethylformamide was added the solution of 1.2 g (2.8 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate in 2 mL of dimethylformamide. The mixture was stirred at room temperature for 2 hour, then diluted with ice water and saturated sodium carbonate. The mixture was extracted with dichloromethane twice. The combined organic layers were washed three times with sodium carbonate, three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-60:40) gave 0.7 g of 4-amino-N-(1-methyl-piperidin-4-yl)-3-trifluoromethoxy-benzamide as a white solid.

Workup

  1. extractionThe mixture was extracted with dichloromethane twice
  2. washThe combined organic layers were washed three times with sodium carbonate, three times with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography
  7. washeluting with dichloromethane-methanol (gradient, 100:0-60:40)

Sources & evidence

ORD record
ord-cad60c0438864d4d9cbe006f4ea3e3ab
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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