Potassium Phosphate, Tribasic → (E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2,3,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401540Notes

Reaction equation

HRID 1401540 reaction equation
[CH3:1][N:2]1[CH:15]([CH3:16])[CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1CCC[C@H:18]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:34]=[CH:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1>CN(C=O)C.[Cu]I>[F:42][C:39]1[CH:40]=[CH:41][C:36](/[C:35](/[CH3:18])=[CH:34]/[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH:15]([CH3:16])[CH2:14][C:5]2=3)=[CH:37][CH:38]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 538551491-(-2-Bromovinyl)-4-fluorobenzeneHCID 666120872,3,8-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 59454983(E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2,3,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

2,3,8-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (107 mg, 0.5 mmol) was dissolved in DMF. Copper (I) iodide (9.5 mg, 0.05 mmol), L-proline (11.5 mg, 0.1 mmol) and potassium phosphate (414 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(2-bromovinyl)-4-fluorobenzene (107.83 mg, 0.55 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 100° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-7% MeOH-DCM. Yield: 92 mg. 1H NMR (CD3OD, oxalate salt) δ (ppm): 7.70 (m, 2H), 7.30 (s, 1H), 7.10 (m, 4H), 6.95 (s, 1H), 4.70 (m, 1H), 4.60 (m, 1H), 3.90 (m, 1H), 3.20 (m, 1H), 2.95 (m, 4H), 2.42 (s, 3H), 1.90 (s, 3H), 1.50 (d, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 100° C. (
  3. temperatureprolonged heating in some cases
  4. customDMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)
  8. washeluting with 0-7% MeOH-DCM

Sources & evidence

ORD record
ord-5a014c17ff45438d802f5600ca1c8c99
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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