1-Bromo-2-methylpropane → HCID 86689299, compound

HRID 537325Notes

Reaction equation

HRID 537325 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH:20]([CH3:22])[CH3:21])[CH:13]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:30][CH:31]([CH3:33])[CH3:32]>CN(C=O)C>[CH2:19]([O:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[O:11][CH2:10][C:2]1[N:3]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=1)[CH:20]([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 11430Potassium CarbonateHCID 86689298HCID 86689298, compound

Product 1

HCID 86689299HCID 86689299, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A 100 mL flask fitted with a stir-bar, condenser, and an Ar inlet was charged with benzimidazole 73 (1.73 g, 5.84 mmol) and K2CO3 (1.62 g, 11.7 mmol). DMF (25 mL) was added followed by 1-bromo-2-methylpropane (1.20 g, 0.95 mL, 8.73 mmol), and the mixture was heated in a 90° C. bath for 5 hr. Another 0.3 mL of 1-bromo-2-methylpropane was added and the mixture was heated overnight. The suspension was cooled, and the solids were filtered off and rinsed with EtOAc (100 mL). The filtrate was washed with saturated aqueous NH4Cl (2×60 mL), H2O (2×60 mL), and brine (50 mL), filtered through phase separation paper, and concentrated in vacuo to a yellow oil. The crude oil was chromatographed on silica gel with the product eluting with 10-12% EtOAc in hexanes. The product fractions were concentrated to give 1.73 g of Compound #17 as a colorless oil (84%). 1H NMR (300 MHz, CDCl3): δ 7.81 (m, 1H), 7.40 (m, 1H), 7.36-7.24 (m, 2H), 7.20 (t, 1H), 6.71-6.63 (m, 2H), 6.56 (dd, 1H), 5.37 (s, 2H), 4.12 (d, 2H), 3.72 (d, 2H), 2.36 (nonet, 1H), 2.08 (nonet, 1H), 1.03 (d, 6H), 0.98 (d, 6H) ppm. HPLC analysis (5:10:85 H2O:A1:MeOH) showed a purity of 99% with a retention time of 8.0 min.

Workup

  1. customA 100 mL flask fitted with a stir-bar, condenser
  2. temperaturethe mixture was heated overnight
  3. temperatureThe suspension was cooled
  4. filtrationthe solids were filtered off
  5. washrinsed with EtOAc (100 mL)
  6. washThe filtrate was washed with saturated aqueous NH4Cl (2×60 mL), H2O (2×60 mL), and brine (50 mL)
  7. filtrationfiltered through phase separation paper
  8. concentrationconcentrated in vacuo to a yellow oil
  9. customThe crude oil was chromatographed on silica gel with the product
  10. washeluting with 10-12% EtOAc in hexanes
  11. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-cb199b0654924cf7af448f806d236ffd
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

Loading…