Ethanethiol → Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-hydroxy-phenyl]methylamino]phenoxy]acetate

HRID 1771783Notes

Reaction equation

HRID 1771783 reaction equation
[F:1][C:2]1[C:15]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([O:24]C)[CH:21]=[C:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)[CH:19]=2)=[C:14]([F:33])[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]([O:8][CH:9]([CH3:11])[CH3:10])=[O:7].[Al+3].[Cl-].[Cl-].[Cl-].C(S)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[C:15]([NH:16][CH2:17][C:18]2[CH:23]=[C:22]([OH:24])[CH:21]=[C:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)[CH:19]=2)=[C:14]([F:33])[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]([O:8][CH:9]([CH3:10])[CH3:11])=[O:7]

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) ChlorideHCID 89443593Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenoxy]acetate

Product 1

HCID 89445486Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-hydroxy-phenyl]methylamino]phenoxy]acetateYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methoxy-phenyl]methylamino]phenoxy]acetate (II(q)) (700 mg, 1.52 mmol, 1.0 eq) in DCM (20 mL) at 0° C. was added AlCl3 (1.2 g, 9.12 mmol, 6.0 eq) and ethanethiol (566 mg, 9.12 mmol, 6.0 eq) under N2. The reaction mixture was stirred at room temperature for 3 h and the resulting mixture was poured into aqueous NaHCO3 and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:20) to give the title compound as a yellow oil (500 mg, 74%).

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. washwas washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:20)

Sources & evidence

ORD record
ord-b53e08c3745649e5aa408f5acde079d4
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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