Water → 2-Morpholinoethyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl) phenyl]methylamino]phenoxy]acetate

HRID 1771776Notes

Reaction equation

HRID 1771776 reaction equation
[F:1][C:2]1[C:12]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH:18]=[CH:17][C:16]=2[F:28])=[C:11]([F:29])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].[O:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37]O)[CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[C:12]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH:18]=[CH:17][C:16]=2[F:28])=[C:11]([F:29])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:37][CH2:36][N:33]1[CH2:34][CH2:35][O:30][CH2:31][CH2:32]1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 611632-MorpholinoethanolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 715155142-[2,4-Difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid

Product 1

HCID 894454442-Morpholinoethyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl) phenyl]methylamino]phenoxy]acetateYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid (I(b)) (800 mg, 1.97 mmol, 1.0 eq), 2-morpholinoethanol (284 mg, 2.17 mmol, 1.1 eq), HATU (974 mg, 2.56 mmol, 1.3 eq), and TEA (598 mg, 5.91 mmol, 3 eq) in DCM (10 mL) and DMF (10 mL) was stirred at room temperature overnight under N2. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with brine, dried (Na2SO4), filtered and evaporated in vacuo and the residue purified by column chromatography, (MeOH:DCM 0:1 to 1:50) to give the title compound as a yellow oil (710 mg, 70%).

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customthe residue purified by column chromatography, (MeOH:DCM 0:1 to 1:50)

Sources & evidence

ORD record
ord-19026ff7d67849a28593ba0fd6e3c02c
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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