Sulfuryl chloride → Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

HRID 913387Notes

Reaction equation

HRID 913387 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.S(Cl)([Cl:24])(=O)=O>C1(C)C=CC=CC=1.C(N)(C)(C)C.S(Cl)(Cl)(=O)=O>[Cl:24][C:3]1[C:2]([OH:1])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:7]2[CH2:11][C:12]([F:15])([F:13])[F:14]

Participants

6

Reactant 2

HCID 24648Sulfuryl chloride2×HCID 24985291Ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

Product 1

HCID 57800334Ethyl 4-chloro-5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylateYield 92%

Reagents, catalysts & solvents 3

HCID 6385Tert-ButylamineCatalyst3×HCID 24648Sulfuryl chlorideCatalystHCID 1140TolueneSolvent2×

Procedure

To a solution of ethyl 5-hydroxy-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate (0.7 g, 2.44 mmol) in toluene (30 mL) was added tert-butyl amine (0.014 g, 0.2 mmol) and the mixture was set in an oil bath preheated at 70° C. After 1 min, a solution of sulfuryl chloride (0.37 g, 2.49 mmol) in toluene (1 mL) was added. The reaction was followed by TLC (60% CH2Cl2-hexanes) and additional reagents were added accordingly. After 30 min, more tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.06 g, 0.37 mmol) were added. After another 30 min additional tert-butylamine (0.014 g, 0.2 mmol) and sulfuryl chloride (0.019 g, 0.12 mmol) were added and heating was continued for 30 min. Upon cooling, the mixture was partitioned between EtOAc and 0.2N HCl. The organic phase was washed with 0.2N HCl and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient) to afford the title compound (0.72 g, 92% yield, 95% purity): MS (ES) m/z 322 (M+1).

Workup

  1. customthe mixture was set in an oil bath
  2. custompreheated at 70° C
  3. additionwere added accordingly
  4. waitAfter 30 min
  5. temperatureheating
  6. waitwas continued for 30 min
  7. temperatureUpon cooling
  8. customthe mixture was partitioned between EtOAc and 0.2N HCl
  9. washThe organic phase was washed with 0.2N HCl
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (10-80% CH2Cl2-hexanes gradient)

Sources & evidence

ORD record
ord-31285f029ba842bca21d6e1fa4f03c41
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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