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

HRID 1771780Notes

Reaction equation

HRID 1771780 reaction equation
[CH:1]([C:12](OCC)=O)([C:7](OCC)=[O:8])[C:2](OCC)=[O:3].[F:17][C:18]1[C:28]([NH:29][CH2:30][C:31]2[CH:36]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)[CH:34]=[CH:33][C:32]=2[F:44])=[C:27]([F:45])[CH:26]=[CH:25][C:19]=1[O:20][CH2:21][C:22]([OH:24])=[O:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[OH:3][CH2:2][CH:1]([CH2:7][OH:8])[CH2:12][O:23][C:22](=[O:24])[CH2:21][O:20][C:19]1[CH:25]=[CH:26][C:27]([F:45])=[C:28]([NH:29][CH2:30][C:31]2[CH:36]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)[CH:34]=[CH:33][C:32]=2[F:44])[C:18]=1[F:17]

Participants

6

Reactant 3

HCID 80471Triethyl methanetricarboxylateHCID 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 89444449[3-Hydroxy-2-(hydroxymethyl)propyl]2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl) phenyl]methylamino]phenoxy]acetateYield 55.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of triethyl methanetricarboxylate (700 mg, 1.73 mmol, 1.0 eq) in DMF (40 mL) was added 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetic acid (I(b)) (367 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), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (DCM:MeOH=100:1-20:1) to give the title compound as a colourless oil (475 mg, 49%).

Workup

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

Sources & evidence

ORD record
ord-f79420b39af644ed82a4f94e6030d00a
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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