Potassium Carbonate → 3-bromo-4-chloro-N-methyl-N-(2-{3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-tetrazol-5-yl]-propoxy}-phenyl)-benzamide

HRID 661662Notes

Reaction equation

HRID 661662 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[Cl:27])[C:5]([N:7]([CH3:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH2:15][CH2:16][CH2:17][C:18]1[NH:22][N:21]=[N:20][N:19]=1)=[O:6].[CH3:28][Si:29]([CH3:36])([CH3:35])[CH2:30][CH2:31][O:32][CH2:33]Cl.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[Cl:27])[C:5]([N:7]([CH3:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH2:15][CH2:16][CH2:17][C:18]1[N:22]([CH2:33][O:32][CH2:31][CH2:30][Si:29]([CH3:36])([CH3:35])[CH3:28])[N:21]=[N:20][N:19]=1)=[O:6].[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[Cl:27])[C:5]([N:7]([CH3:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[O:14][CH2:15][CH2:16][CH2:17][C:18]1[NH:22][N:21]([CH2:33][O:32][CH2:31][CH2:30][Si:29]([CH3:36])([CH3:35])[CH3:28])[NH:20][N:19]=1)=[O:6]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178485344HCID 178485344, compound

Product 2

HCID 686037923-bromo-4-chloro-N-methyl-N-(2-{3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-tetrazol-5-yl]-propoxy}-phenyl)-benzamideHCID 686048533-bromo-4-chloro-N-methyl-N-(2-{3-[2-(2-trimethylsilanyl-ethoxymethyl)-1H-tetrazol-5-yl]-propoxy}-phenyl)-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3-bromo-4-chloro-N-methyl-N-{2-[3-(1H-tetrazol-5-yl)-propoxy]-phenyl}-benzamide (1.90 g, 4.2 mmol) in DMF (20 mL) was added 2-(trimethylsilyl)ethoxymethyl chloride (0.89 mL, 5.1 mmol) in one portion, followed by addition of K2CO3 (1.16 g, 8.4 mmol). The mixture was stirred at room temperature for approximately 16 hrs and then was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, and was dried over MgSO4. The filtrate was then concentrated in vacuo and the residue purified by silica gel column chromatography (eluent: 30% ethyl acetate in hexane) to afford 3-bromo-4-chloro-N-methyl-N-(2-{3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-tetrazol-5-yl]-propoxy}-phenyl)-benzamide and 3-bromo-4-chloro-N-methyl-N-(2-{3-[2-(2-trimethylsilanyl-ethoxymethyl)-1H-tetrazol-5-yl]-propoxy}-phenyl)-benzamide as two regioisomers (upper spot: 736 mg and lower spot: 785 mg). MS [M+H]+: 582.0; tR=2.92 min. (method 1) for upper spot and MS [M+H]+: 582.0; tR=2.75 min. (method 1) for lower spot.

Workup

  1. customwas partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialwas dried over MgSO4
  5. concentrationThe filtrate was then concentrated in vacuo
  6. customthe residue purified by silica gel column chromatography (eluent: 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8d52749e1c4748a18b21857f85c0ea5b
Source dataset
uspto-grants-2011_12
Patent number
US08084614B2

Reaction notes

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