Sulfuric Acid → HCID 45375942, compound

HRID 1401467Notes

Reaction equation

HRID 1401467 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH:11](O)[CH:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[CH3:13])[C:6]3[CH2:22][CH2:23][N:24]([CH3:26])[CH2:25][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:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)\[CH3:13])[C:6]3[CH2:22][CH2:23][N:24]([CH3:26])[CH2:25][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 67310821HCID 67310821, compound

Product 1

HCID 45375942HCID 45375942, compound

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(4-fluorophenyl)propan-1-ol (1 g, 2.68 mmol, 1 equiv.) was refluxed with 25% sulfuric acid (7 mL) for 2 h, cooled to RT and then cooled to 5° C. in ice-water bath. 15% aqueous solution of KOH was added dropwise to the reaction mixture (pH 9-10), followed by extraction with EtOAc (3×10 mL). The combined organic extracts were washed with water (10 mL) followed by brine, dried over sodium sulfate and evaporated under vacuum and purified by column chromatography using 100-200 silica gel, using a gradient of MeOH-EtOAc (0-10%) to obtain a mixture of isomers (150 mg), which was separated by HPLC. Yield: 15 mg. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.68 (t, 2H), 7.54 (s, 1H), 7.21 (s, 2H), 7.16 (t, 2H), 6.97 (s, 1H), 4.8 (bs, 1H), 4.39 (bs, 1H), 3.85 (bs, 1H), 3.60 (bs, 1H), 3.13 (bs, 5H), 1.92 (s, 3H).

Workup

  1. extractionfollowed by extraction with EtOAc (3×10 mL)
  2. washThe combined organic extracts were washed with water (10 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated under vacuum
  5. custompurified by column chromatography
  6. customto obtain
  7. additiona mixture of isomers (150 mg), which
  8. customwas separated by HPLC

Sources & evidence

ORD record
ord-93abe5f257644441bcc86d3423592c52
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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