Sulfuric Acid → HCID 59455019, compound

HRID 1401501Notes

Reaction equation

HRID 1401501 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)(O)[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][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:16]=[N:17][CH:18]=[CH:19][CH:20]=3)\[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 49779774HCID 49779774, compound

Product 1

HCID 59455019HCID 59455019, compound

Conditions

Temperature
5 °C

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol (1 g, 2.81 mmol, 1 equiv.) was refluxed with 25% sulfuric acid (7 mL) for 2 h. The reaction mixture was cooled to 5° C. in an 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 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. 1HNMR (DMSO, TFA salt) δ (ppm): 8.90 (s, 1H), 8.60 (d, 1H), 8.10 (d, 1H), 7.50 (m, 2H), 7.22 (d, 2H), 7.10 (d, 1H), 3.6 (m, 2H), 2.70 (m, 4H), 2.45 (s, 3H), 1.90 (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-3b27f8a3f82b44518c8da2646e0fcc4c
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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