Pentaerythritol → [3-Hydroxy-2,2-bis(hydroxymethyl)propyl]2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluoro phenyl)phenyl]methylamino]phenoxy]acetate

HRID 1771779Notes

Reaction equation

HRID 1771779 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].[OH:30][CH2:31][C:32]([CH2:37]O)([CH2:35][OH:36])[CH2:33][OH:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[OH:30][CH2:31][C:32]([CH2:35][OH:36])([CH2:33][OH:34])[CH2:37][O:7][C:6](=[O:8])[CH2:5][O:4][C:3]1[CH:9]=[CH:10][C:11]([F:29])=[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:2]=1[F:1]

Participants

6

Reactant 3

HCID 8285PentaerythritolHCID 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 89445456[3-Hydroxy-2,2-bis(hydroxymethyl)propyl]2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluoro phenyl)phenyl]methylamino]phenoxy]acetateYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid (I(b)) (700 mg, 1.73 mmol, 1.0 eq) in DMF (30 mL) was added pentaerythritol (470 mg, 3.45 mmol, 2.0 eq), TEA (699 mg, 6.91 mmol, 4.0 eq) and HATU (985 mg, 2.60 mmol, 1.5 eq). The resulting mixture was stirred at room temperature overnight under N2. The reaction was diluted with water then extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography (DCM:MeOH=100:1-20:1) to give the title compound as a colourless oil (370 mg, 41%).

Workup

  1. extractionthen extracted with EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography (DCM:MeOH=100:1-20:1)

Sources & evidence

ORD record
ord-4f98b6eba89e442f89546df46b4d317c
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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