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

HRID 1771700Notes

Reaction equation

HRID 1771700 reaction equation
[F:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH:20]=[C:19]([CH3:30])[C:18]=2[O:31]C)=[C:13]([F:33])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[Al+3].[Cl-].[Cl-].[Cl-].CCS>C(Cl)Cl>[F:1][C:2]1[C:14]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH:20]=[C:19]([CH3:30])[C:18]=2[OH:31])=[C:13]([F:33])[CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 6451240Aluminum(III) ChlorideHCID 89443764Ethyl 2-[2,4-difluoro-3-[[5-(3-fluorophenyl)-2-methoxy-3-methyl-phenyl]methylamino]phenoxy]acetate

Product 1

HCID 89443786Ethyl 2-[2,4-difluoro-3-[[5-(3-fluorophenyl)-2-hydroxy-3-methyl-phenyl]methylamino]phenoxy]acetateYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 2-[2,4-difluoro-3-[[5-(3-fluorophenyl)-2-methoxy-3-methyl-phenyl]methylamino]phenoxy]acetate (see example 20) (190 mg, 0.414 mmol, 1.0 eq) in DCM (5 mL) at 0° C. under N2 was added AlCl3 (330.8 mg, 2.48 mmol, 6.0 eq) and EtSH (154.2 mg, 2.48 mmol, 6.0 eq). The resulting mixture was stirred for 1.5 h at room temperature then the reaction was quenched by dropwise addition of water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc 1:0 to 10:1 v/v) to give the title compound as an oil (90 mg, 49%).

Workup

  1. customthe reaction was quenched by dropwise addition of water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic extracts were washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue obtained
  8. customwas purified by column chromatography (petroleum ether:EtOAc 1:0 to 10:1 v/v)

Sources & evidence

ORD record
ord-9eaf6bd2aa5f44999c39eed02b9ff087
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

Loading…