Potassium bis(trimethylsilyl)amide → 2,6-Dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester

HRID 593516Notes

Reaction equation

HRID 593516 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:29]([O:31][C:32](=[O:43])[C:33]1[C:38]([CH3:39])=[CH:37][C:36]([CH2:40]Br)=[CH:35][C:34]=1[CH3:42])[CH3:30]>C1COCC1>[CH2:29]([O:31][C:32](=[O:43])[C:33]1[C:38]([CH3:39])=[CH:37][C:36]([CH2:40][N:8]2[C:9]3[C:5](=[CH:4][C:3]([Cl:2])=[CH:11][CH:10]=3)[C:6]([CH3:18])=[C:7]2[C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[CH:35][C:34]=1[CH3:42])[CH3:30]

Participants

5

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539625-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochlorideHCID 582156744-Bromomethyl-2,6-dimethyl-benzoic acid ethyl ester

Product 1

HCID 582156242,6-Dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

5-Chloro-3-methyl-2-pyridin-3-yl-1H-indole (Example 2, 1.350 g, 4.659 mmol) is suspended in THF (40 mL) and cooled to 0° C. KHMDS (0.5M in toluene, 32.6 mL, 16.3 mmol) is added dropwise. After 1 h, 4-bromomethyl-2,6-dimethyl-benzoic acid ethyl ester (4.95 g, 18.2 mmol) in THF (10 mL) is added dropwise. The mixture is allowed to warm to room temperature overnight. The mixture is then quenched with saturated aqueous ammonium chloride and diluted with dichloromethane. The aqueous phase is extracted with ethyl acetate, dried over MgSO4, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography (dichloromethane-methanol, 1:0 to 99:1 to 49:1 to 97:3) affords 2,6-dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester as an orange solid. MS (ESI) m/z 399 (M+H)+.

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe mixture is then quenched with saturated aqueous ammonium chloride
  3. additiondiluted with dichloromethane
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by silica gel chromatography (dichloromethane-methanol, 1:0 to 99:1 to 49:1 to 97:3)

Sources & evidence

ORD record
ord-d5f7471c056449d19521b2e6933ada6d
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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