Benzyl Bromide → 1-[5-Chloro-1-(phenylmethyl)-1h-indol-2-yl]pentan-1-one

HRID 1818621Notes

Reaction equation

HRID 1818621 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])=[CH:5]2.[H-].[Na+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:6]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])=[CH:5]2

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 674821881-(5-chloro-1H-indol-2-yl)pentan-1-one

Product 1

HCID 674823471-[5-Chloro-1-(phenylmethyl)-1h-indol-2-yl]pentan-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound of Example 3 Step A (1.35 g, 5.73 mmol) in DMF (25 mL) was added NaH (252 mg, 60% suspension if mineral oil, 6.30 mmol). After 20 min, benzyl bromide (0.750 mL, 6.30 mmol) was added, and the mixture was allowed to stir for 15 h, whereupon it was quenched by addition of sat. aq. NH4Cl. The aqueous phase was extracted with EtOAc, and the organic phase was dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 15%, then 15 to 100% EtOAc in hexanes) provided the title compound: LCMS A, tr=4.36 min, m/z 326.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=1.0 Hz, 1H), 7.34-7.22 (m, 6 H), 7.04 (d, J=7.0 Hz, 2H), 5.88 (s, 2H), 2.99 (t, J=7.5 Hz, 2H), 1.76-1.70 (m, 2H), 1.44-1.36 (m, 2 H), 0.97 (t, J=7.0 Hz, 3H).

Workup

  1. customwas quenched by addition of sat. aq. NH4Cl
  2. extractionThe aqueous phase was extracted with EtOAc
  3. dry with materialthe organic phase was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel (0 to 15%

Sources & evidence

ORD record
ord-a4f0382ddffc4a838a19996c7f23f850
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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