Sodium hydride → Methyl 4-{[(4-tert-butylcyclohexyl)(1-{2-[(trimethylsilyl)oxy]ethyl}-1H-benz-imidazol-2-yl)amino]methyl}benzoate

HRID 229993Notes

Reaction equation

HRID 229993 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1)[CH:11]1[CH2:16][CH2:15][CH:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][CH2:12]1.[H-].[Na+].Br[CH2:35][CH2:36][O:37][Si:38]([CH3:41])([CH3:40])[CH3:39]>C1COCC1.CN(C=O)C>[C:17]([CH:14]1[CH2:15][CH2:16][CH:11]([N:10]([CH2:21][C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=2)[C:2]2[N:3]([CH2:35][CH2:36][O:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH2:12][CH2:13]1)([CH3:18])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 587231(2-Bromoethoxy)trimethylsilaneHCID 68837482Methyl 4-{[1H-benzimidazol-2-yl(4-tert-butylcyclohexyl)amino]methyl}-benzoate

Product 1

HCID 68838381Methyl 4-{[(4-tert-butylcyclohexyl)(1-{2-[(trimethylsilyl)oxy]ethyl}-1H-benz-imidazol-2-yl)amino]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To the title compound from Example 1 Step C (0.5 mmol, 210 mg) in 1 mL of THF was added a solution of NaH (1 mmol, 40 mg of 60% slurry in mineral oil) in 1 mL of DMF (exothermic, H2 evolution). After gas evolution ceased for several minutes, (2-bromoethoxy)(trimethyl)silane was added to the solution via syringe. The reaction mixture was heated to 40° C. After 2.5 h the reaction was quenched by addition of saturated ammonium chloride. The product was extracted 3× with EtOAc and the organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica eluting with 5% EtOAc/hexanes. HPLC A: 3.14 min.

Workup

  1. waitAfter gas evolution ceased for several minutes
  2. customAfter 2.5 h the reaction was quenched by addition of saturated ammonium chloride
  3. extractionThe product was extracted 3× with EtOAc
  4. dry with materialthe organic phase was dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography on silica eluting with 5% EtOAc/hexanes
  7. custom3.14 min.

Sources & evidence

ORD record
ord-f277645e9356496790976fdc1ffd5da5
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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