Hydrochloric Acid → 5-methoxy-7-methyl-3-(1-methylpiperidin-4-yl)-1H-indole

HRID 1766234Notes

Reaction equation

HRID 1766234 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[C:6]2[C:13]1[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH:18]=1.[BH4-].[Na+].FC(F)(F)C(O)=O.Cl.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 179800975-Methoxy-7-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Product 1

HCID 179800985-methoxy-7-methyl-3-(1-methylpiperidin-4-yl)-1H-indoleYield 76%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 5-methoxy-7-methyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (0.1 mole, 24.71 g) in tetrahydrofuran (295 mL) at room temperature was added sodium borohydride (0.2 mole, 7.29 g). Trifluoroacetic acid (0.3 mole, 32.97 g) was added over a 15 minute period. The reaction was stirred at room temperature for 1.5 hours. To the heavy suspension was added 5N hydrochloric acid (200 mL). The resulting solution was stirred at room temperature for 1.5 hours. To the reaction was added ethyl acetate (500 mL) then the pH was adjusted to >12 with 50% wt/wt sodium hydroxide. The phases were separated and the aqueous phase was extracted with ethyl acetate (2×500 mL). The organic phases were combined, dried over sodium sulfate then filtered. The filtrate was filtered through a pad of silica (height of silica=7.0 cm) in a scinter glass funnel (inner diameter of funnel=14.5 cm). After the first fraction was collected the next two fractions were eluted with chloroform (1.2 L each). The remaining fractions were eluted with 90:10:1 chloroform:methanol:ammonium hydroxide (1.2 L fractions collected). The desired fractions were combined and concentrated in vacuo to afford 18.94 g (76%) of the title compound as a white solid: mass spectrum (ion spray): m/z=259 (M+1); 1H NMR (DMSOd6): 7.02 (d, 1H), 6.81 (d, 1H), 6.53 (d, 1H), 3.74 (s, 3H), 2.84 (m, 2H), 2.62 (m, 1H), 2.39 (s, 3H), 2.23 (s, 3H), 2.06 (m, 2H), 1.90 (m, 2H), 1.67 (m, 2H).

Workup

  1. stirringThe resulting solution was stirred at room temperature for 1.5 hours
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×500 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationthen filtered
  6. filtrationThe filtrate was filtered through a pad of silica (height of silica=7.0 cm) in a scinter glass funnel (inner diameter of funnel=14.5 cm)
  7. customAfter the first fraction was collected the next two fractions
  8. washwere eluted with chloroform (1.2 L each)
  9. washThe remaining fractions were eluted with 90:10:1 chloroform
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-66b71de3e8b04b4ead2caec2cf086025
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

Loading…