1-Bromo-2-methylpropane → HCID 18878949, compound

HRID 537317Notes

Reaction equation

HRID 537317 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]2[NH:10][C:11]3[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=3[N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:25][CH:26]([CH3:28])[CH3:27]>CN(C=O)C>[CH2:25]([N:13]1[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[N:10]=[C:9]1[CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH:26]([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane3×HCID 11430Potassium Carbonate2×HCID 2910532-(2-phenylethyl)-1H-benzimidazole

Product 1

HCID 18878949HCID 18878949, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A 100 mL flask fitted with a stir-bar and septum with an Ar inlet was charged with benzimidazole 67 (2.00 g, 9.00 mmol) and K2CO3 (2.49 g, 18.0 mmol). DMF (25 mL) was added followed by 1-bromo-2-methylpropane (1.84 g, 1.47 mL, 13.5 mmol), and the mixture was heated in a 90° C. bath overnight. Another 1 mL of 1-bromo-2-methylpropane was added and the mixture was heated overnight again. Another addition of 1 mL of 1-bromo-2-methylpropane and 1 g K2CO3 was executed, and the mixture was heated overnight again. The suspension was cooled, and the solids were filtered off and rinsed with EtOAc (80 mL). The filtrate was washed with saturated NH4Cl (2×50 mL), H2O (2×50 mL), and brine (30 mL), filtered through phase separation paper, and concentrated in vacuo to an orange oil. The crude oil was filtered through a plug of silica gel with CH2Cl2 (100 mL). The filtrate was concentrated in vacuo to give 1.60 g of Compound #14 as a yellow oil (64%). 1H NMR (300 MHz, CDCl3): δ 7.80 (m, 1H), 7.35-7.21 (m, 8H), 3.81 (d, 2H), 3.35-3.26 (m, 2H), 3.22-3.13 (m, 2H), 2.16 (nonet, 1H), 0.95 (d, 6H) ppm. HPLC analysis (5:10:85 H2O:A1:MeOH) showed a purity of 96% with a retention time of 4.7 min.

Workup

  1. customA 100 mL flask fitted with a stir-bar
  2. temperaturethe mixture was heated overnight again
  3. temperaturethe mixture was heated overnight again
  4. temperatureThe suspension was cooled
  5. filtrationthe solids were filtered off
  6. washrinsed with EtOAc (80 mL)
  7. washThe filtrate was washed with saturated NH4Cl (2×50 mL), H2O (2×50 mL), and brine (30 mL)
  8. filtrationfiltered through phase separation paper
  9. concentrationconcentrated in vacuo to an orange oil
  10. filtrationThe crude oil was filtered through a plug of silica gel with CH2Cl2 (100 mL)
  11. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-1ca733394a2a4d728aa8963937f0e89a
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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