Morpholine → (1-Benzyl-3-bromo-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone

HRID 623789Notes

Reaction equation

HRID 623789 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:34]([N:41]1[C:45]([C:46]([F:49])([F:48])[F:47])=[C:44]([CH3:50])[C:43]([Br:51])=[C:42]1[C:52]([OH:54])=O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[NH:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1>CN(C=O)C.CCOC(C)=O.O>[CH2:34]([N:41]1[C:45]([C:46]([F:47])([F:48])[F:49])=[C:44]([CH3:50])[C:43]([Br:51])=[C:42]1[C:52]([N:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1)=[O:54])[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867118651-Benzyl-3-bromo-4-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 86711874(1-Benzyl-3-bromo-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanoneYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (12.59 g 33.14 mmol) and DIPEA (12.3 mL, 33.14 mmol) were added to the ice cold solution of 1-benzyl-3-bromo-4-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylic acid (10 g, 27.62 mmol) in DMF (110 mL) and it was stirred for 10 min at same temperature and then morpholine (2.8 mL, 33.14 mmol) was added to the reaction mixture warmed to RT and then stirred for 14 h. The reaction mixture was diluted with EtOAc and H2O. The aqueous layer was extracted with EtOAc (2×300 mL), washed with water (2×300 mL) and brine (2×300 mL), organic layer was dried over anhydrous Na2SO4, combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield crude mass which was then purified by column chromatography (100-200 mesh Silica gel; 30% ethyl acetate/hexane; Rf-value 0.6) to afford title compound (10 g, 84% yield, white color solid).

Workup

  1. stirringstirred for 14 h
  2. extractionThe aqueous layer was extracted with EtOAc (2×300 mL)
  3. washwashed with water (2×300 mL) and brine (2×300 mL), organic layer
  4. dry with materialwas dried over anhydrous Na2SO4
  5. dry with materialwas dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto yield crude mass which
  8. customwas then purified by column chromatography (100-200 mesh Silica gel; 30% ethyl acetate/hexane; Rf-value 0.6)

Sources & evidence

ORD record
ord-76a414e6f0474300864a3ee493e0cf6e
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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