Sodium hydride → 4-(4-Chlorophenyl)-3-(1-methyl-1H-indol-4-yl)-butan-2-one

HRID 30387

Reaction equation

HRID 30387 reaction equation
[H-].[Na+].[CH3:3][N:4]1[C:12]2[C:7](=[C:8]([CH2:13][C:14]([CH3:16])=[O:15])[CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5]1.[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>C1COCC1>[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][CH:13]([C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:7]=2[CH:6]=[CH:5][N:4]3[CH3:3])[C:14](=[O:15])[CH3:16])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 222704771-(1-methyl-1H-indol-4-yl)propan-2-one

Product 1

HCID 222703994-(4-Chlorophenyl)-3-(1-methyl-1H-indol-4-yl)-butan-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of 135 mg (3.38 mmol) of sodium hydride in 8 mL dry THF, a solution of 605 mg (3.23 mmol) 1-(1-methyl-1H-indol-4-yl)acetone in 2 mL THF was added. The mixture was stirred for 45 min during which time the sodium hydride dissolved and a yellow orange solution resulted. The reaction was cooled in ice bath and 660 mg (3.24 mmol) 4-chlorobenzyl bromide in 1 mL THF was added. The cold bath was removed and the solution was stirred for 1.5 h. The reaction was quenched with 1.2 N HCl and extracted with EtOAc. The organic layer was washed with brine, dried and concentrated. The residue was chromatographed using a gradient of 10-20% EtOAc/hexane to isolate the desired product. 1H NMR: (500 MHz, CDCl3): δ 2.03 (s, 3H), 3.07 (m, 1H), 3.58 (m, 1H), 3.84 (s, 3H), 4.23 (t, 1H), 6.52 (d, 1H), 6.9-7.3 (m, 8H).

Workup

  1. dissolutiondissolved
  2. customa yellow orange solution resulted
  3. temperatureThe reaction was cooled in ice bath
  4. customThe cold bath was removed
  5. customThe reaction was quenched with 1.2 N HCl
  6. extractionextracted with EtOAc
  7. washThe organic layer was washed with brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was chromatographed

Sources & evidence

ORD record
ord-c1b44180c204478e819602e59cdeda70
Source dataset
uspto-grants-2008_09
Patent number
US07423067B2

Linked notes

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