4-(Morpholine-4-carbonyl)aniline → HCID 66604956, compound

HRID 2410701Notes

Reaction equation

HRID 2410701 reaction equation
CC([O-])(C)C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])=[CH:10][CH:9]=1.[Br:22][C:23]1[CH:24]=[CH:25][C:26](F)=[C:27]([CH:30]=1)[C:28]#[N:29]>CS(C)=O>[Br:22][C:23]1[CH:24]=[CH:25][C:26]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[O:15])=[CH:12][CH:13]=2)=[C:27]([CH:30]=1)[C:28]#[N:29]

Participants

5

Reactant 3

HCID 5778154-(Morpholine-4-carbonyl)anilineHCID 27249005-Bromo-2-fluorobenzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 66604956HCID 66604956, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent3×

Procedure

KOtBu (2.78 g, 24.75 mmol) was dissolved into 20 ml DMSO in a round bottom flask. (4-aminophenyl)(morpholino)methanone (5.10 g, 24.75 mmol) in 10 ml DMSO was added and the resulting mixture was stirred for 35 mins at r.t. The mixture was cooled in an iced bath for 5 mins 5-bromo-2-fluorobenzonitrile (4.5 g, 22.50 mmol) in 10 ml DMSO was added dropwise. Iced bath was removed and the mixture was stirred for 1 hr at r.t. The mixture was diluted with ethyl acetate, 100 ml saturated NH4Cl water solution was added. The organic layer was separated. The water layer was extracted with ethyl acetate. The organic layers were combined and washed with H2O (4×), brine, dried over MgSO4 and concentrated. 8 g crude product (84% purity) was obtained. MS (ESI) m/z 386 (M+H)−. 1H NMR (CDCl3) δ ppm 7.61 (d, 1H, J=2.3), 7.47 (dd, 1H, J=9, 2.5), 7.41 (m, 2H), 7.15 (m, 3H), 6.35 (bs, 1H), 3.65 (bm, 8H).

Workup

  1. additionwas added dropwise
  2. customIced bath was removed
  3. stirringthe mixture was stirred for 1 hr at r.t
  4. additionThe mixture was diluted with ethyl acetate, 100 ml saturated NH4Cl water solution
  5. additionwas added
  6. customThe organic layer was separated
  7. extractionThe water layer was extracted with ethyl acetate
  8. washwashed with H2O (4×), brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-35848d338813408e9377344fb3723278
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…