Chloroacetyl chloride → N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-5-carboxamide

HRID 1505207Notes

Reaction equation

HRID 1505207 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:20]=[CH:19][C:6]([CH2:7][NH:8][C:9](=[O:18])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[C:11]=2[NH2:17])=[C:5]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:4]=1.Cl[CH2:30][C:31](Cl)=[O:32].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:28][C:2]([F:1])([F:27])[C:3]1[CH:20]=[CH:19][C:6]([CH2:7][NH:8][C:9]([C:10]2[C:11]3[NH:17][C:31](=[O:32])[CH2:30][O:16][C:12]=3[CH:13]=[CH:14][CH:15]=2)=[O:18])=[C:5]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:4]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 67425570N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-2-amino-3-hydroxybenzamide

Product 1

HCID 53477039N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-5-carboxamideYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-2-amino-3-hydroxybenzamide 22b (2.5 g, 6.4 mmol) was dissolved in 20 ml of DMF and at 0° C. TEA (1.8 ml, 2 equiv.) and chloroacetyl chloride (0.6 ml, 1.2 equiv.) were added. The mixture was stirred at rt for 2 hours. K2CO3 (1.77 g, 2 equiv.) was added and the reaction was stirred at rt for 20 hours. The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column using AcOEt 1/petroleum ether 1 as eluant gave 1 g of a white solid. Yield=36% 1HNMR (DMSO, 200 MHz) δ 1.57 (2H, bs), 1.69 (4H, bs), 2.82 (4H, m), 4.60 (2H, d, J=5.4 Hz), 4.67 (2H, s), 7.09 (1H, t, J=7.8 Hz), 7.20 (1H, dd, J=8 Hz, J′=1.2 Hz), 7.33 (1H, m), 7.41 (2H, m), 7.57 (1H, m), 9.38 (1H, bt), 11.02 (1H, bs); [M+1] 434.3 (C22H22F3N3O3 requires 433.4).

Workup

  1. stirringthe reaction was stirred at rt for 20 hours
  2. customThe solvent was evaporated
  3. dissolutionthe crude was dissolved in AcOEt (30 ml)
  4. washwashed with water (1×20 ml) and brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-fd55464cf84c4fae8fd0ae79ccf2d504
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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