Chloroacetyl chloride → N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-8-carboxamide

HRID 1505209Notes

Reaction equation

HRID 1505209 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]([NH2:16])[C:11]=2[OH: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[O:17][CH2:30][C:31](=[O:32])[NH: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 67424346N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-amino-2-hydroxybenzamide

Product 1

HCID 53477040N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-8-carboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-amino-2-hydroxybenzamide 24b (830 mg, 2.1 mmol) was dissolved in 10 ml of DMF and at 0° C. TEA (0.58 ml, 2 equiv.) and chloroacetyl chloride (0.2 ml, 1.2 equiv.) were added. The mixture was stirred at rt for 2 hours. K2CO3 (580 mg, 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 460 mg of a white solid. Yield=50% 1HNMR (DMSO, 200 MHz) δ 1.57 (2H, bs), 1.69 (4H, bs), 2.84 (4H, m), 4.58 (2H, d, J=5.2 Hz), 4.69 (2H, s), 7.03 (2H, m), 7.30 (2H, m), 7.45 (2H, m), 8.70 (1H, bt), 10.85 (1H, bs); [M+1] 434.1 (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-5c667cb36c544955b791ead3a639f50b
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

Loading…