Sulfuric Acid → HCID 68485735, compound

HRID 1400409Notes

Reaction equation

HRID 1400409 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])(O)[CH3:13])[C:6]3[CH2:23][CH2:24][N:25]([CH3:27])[CH2:26][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[C:12](\[C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])/[CH3:13])[C:6]3[CH2:23][CH2:24][N:25]([CH3:27])[CH2:26][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 57875876HCID 57875876, compound

Product 1

HCID 68485735HCID 68485735, compound

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(2,4-dichlorophenyl)propan-2-ol (1 g, 2.36 mmol, 1 equiv.) was refluxed with 25% sulfuric acid (7 mL) for 2 h. The reaction mixture was cooled to 5° C. in ice-water bath. KOH (15% aqueous solution) was added dropwise to the reaction mixture until pH 9-10 was achieved. The reaction mixture was extracted with EtOAc (3×10 mL). The combined organic layer was washed with water (10 mL) followed by brine, dried over sodium sulfate and evaporated under vacuum. The crude product was purified by silica gel chromatography (100-200 mesh) using a gradient of MeOH-EtOAc (0-10%) to obtain a mixture of isomers, which were separated by HPLC. 1H NMR (CDCl3, TFA salt) δ (ppm): 7.30 (m, 2H), 7.18 (d, 1H), 7.15 (d, 1H), 7.0 (d, 1H), 6.80 (d, 1H), 6.70 (s, 1H), 4.70 (m, 1H), 4.05 (m, 1H), 3.80 (m, 1H), 3.30 (m, 1H), 3.05 (m, 1H), 2.98 (s, 3H), 2.90 (m, 1H), 2.30 (s, 3H).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3×10 mL)
  2. washThe combined organic layer was washed with water (10 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated under vacuum
  5. customThe crude product was purified by silica gel chromatography (100-200 mesh)
  6. customto obtain
  7. additiona mixture of isomers, which
  8. customwere separated by HPLC

Sources & evidence

ORD record
ord-c59b855b9b3d437aadeaf33f39479e81
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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