2-Amino-4-(trifluoromethyl)pyridine → 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide

HRID 62462Notes

Reaction equation

HRID 62462 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[CH3:12][C:13]1([CH3:29])[C:17]([CH3:19])([CH3:18])[O:16][B:15]([C:20]2[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=2)[O:14]1>CN(C)C1C=CN=CC=1.C(#N)C>[CH3:18][C:17]1([CH3:19])[C:13]([CH3:12])([CH3:29])[O:14][B:15]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([NH:1][C:2]3[CH:7]=[C:6]([C:8]([F:9])([F:11])[F:10])[CH:5]=[CH:4][N:3]=3)=[O:25])=[CH:22][CH:21]=2)[O:16]1

Participants

5

Reactant 2

HCID 27783152-Amino-4-(trifluoromethyl)pyridineHCID 579816664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride

Product 1

HCID 712227974-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To the stirred solution of 2-amino-4-(trifluoromethyl)pyridine (10.79 g, 66.6 mmol) and 4-dimethylaminopyridine (7.39 g, 60.5 mmol) in Acetonitrile (125.00 ml) was added a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride (16.12 g, 60.50 mmol) in Acetonitrile (75.00 ml) dropwise at room temperature. The solution turned into suspension after about half an hour and was stirred at r. t. overnight. The reaction mixture was concentrated and partitioned between 250 ml 0.2 N HCl and 250 ml CH2Cl2. The organic phase was separated and washed with 2×250 ml 0.2N HCl. The organic phase was dried over MgSO4 and evaporated to dryness. The crude was purified on RediSep 220 g silica cartridge and eluted with 1 lt Hexane, 4 lt 10% EtOAc/Hexane, 4 lt 20% EtOAc/Hexane gave white solid product 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide. 1HNMR (CD3Cl, 500 MHz, δ): 8.83 (1H, br), 8.71 (1H, s), 8.45 (1H, d), 7.93 (4H, m), 7.30 (1H, d), 1.38 (12H, s).

Workup

  1. waitThe solution turned into suspension after about half an hour
  2. customovernight
  3. concentrationThe reaction mixture was concentrated
  4. custompartitioned between 250 ml 0.2 N HCl and 250 ml CH2Cl2
  5. customThe organic phase was separated
  6. washwashed with 2×250 ml 0.2N HCl
  7. dry with materialThe organic phase was dried over MgSO4
  8. customevaporated to dryness
  9. customThe crude was purified on RediSep 220 g silica cartridge
  10. washeluted with 1 lt Hexane, 4 lt 10% EtOAc/Hexane, 4 lt 20% EtOAc/Hexane

Sources & evidence

ORD record
ord-c3b33109081d4a0dae571a237958d841
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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