Sulfuric Acid → HCID 59454922, compound

HRID 1400410Notes

Reaction equation

HRID 1400410 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 59454922HCID 59454922, 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. 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 reduced pressure. 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): 7.50 (d, 1H), 7.40 (d, 1H), 7.36-7.20 (m, 4H), 6.55 (d, 1H), 4.78 (m, 1H), 4.10 (m, 1H), 3.90 (m, 1H), 3.40 (m, 3H), 3.0 (s, 3H), 1.80 (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 reduced pressure
  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-e033883fec7845e189998732bcc1fe0f
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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