Phenacyl bromide → 2-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-phenylethanone

HRID 1773246Notes

Reaction equation

HRID 1773246 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.[OH-].[K+].Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:21]>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:19][C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:21])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6259Phenacyl bromideHCID 14797Potassium HydroxideHCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole

Product 1

HCID 497793752-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-phenylethanoneYield 17.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (220 mg, 10 mmol) was dissolved in NMP (2 mL). KOH (560 mg, 0.010 mol) was then added, followed by addition of 2-bromoacetophenone (199 mg, 0.001 mol). The reaction was kept overnight at RT and was monitored by TLC & LC/MS. The reaction was quenched by adding water, and extracted using EtOAc, which was then washed with water (2-3×). The organic layer was dried over sodium sulfate and then concentrated to yield 60 mg of dark brown crude oil that was purified by column chromatography using 100-200 mesh silica gel with 4% MeOH:DCM as eluent. 1HNMR (CDCl3, TFA salt) d (ppm): 8.0 (m, 2H), 7.70 (m, 1H), 7.60 (m, 2H), 7.40 (d, 1H), 7.20 (m, 1H), 7.05 (m, 1H), 5.60 (m, 1H), 5.38 (m, 1H), 4.80 (m, 1H), 4.20 (m, 1H), 3.90 (m, 1H), 3.40 (m, 2H), 3.05 (s, 3H), 1.90 (m, 1H).

Workup

  1. customThe reaction was quenched
  2. additionby adding water
  3. extractionextracted
  4. washwas then washed with water (2-3×)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c22089f8c4c04b6cb874ac4ac0cd4065
Source dataset
uspto-grants-2016_02
Patent number
US09255094B2

Reaction notes

Loading…