Sulfuric Acid → HCID 59455072, compound

HRID 1401470Notes

Reaction equation

HRID 1401470 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]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)(O)[CH3:13])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][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]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)\[CH3:13])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 49779708HCID 49779708, compound

Product 1

HCID 59455072HCID 59455072, compound

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(3-fluoro-4-methoxyphenyl)propan-2-ol (1 g, 2.48 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 (DMSO-d6, oxalate salt) δ (ppm): 7.60 (m, 2H), 7.43 (m, 1H), 7.22-7.15 (m, 4H), 4.40 (m, 2H), 3.80 (s, 3H), 3.10 (m, 4H), 2.80 (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 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-d869b8aaa8124a99bdce0fb0439ac14a
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

Loading…