1-Bromo-2-methylpropane → HCID 709615, compound

HRID 537308Notes

Reaction equation

HRID 537308 reaction equation
[O:1]([CH2:8][C:9]1[NH:13][C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:26]([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 65551-Bromo-2-methylpropane2×HCID 11430Potassium CarbonateHCID 2100742-(Phenoxymethyl)-1H-benzimidazole

Product 1

HCID 709615HCID 709615, compoundYield 81.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A 500 mL flask fitted with a stir-bar, addition funnel, and Ar inlet was charged with 2-(phenoxymethyl)-1H-benzimidazole (61) (10.0 g, 44.6 mmol) and K2CO3 (12.3 g, 89.2 mmol). DMF (120 mL) was added followed by 1-bromo-2-methylpropane (9.17 g, 66.9 mmol). The suspension was heated in a 90° C. bath for 18 hr. Another 900 mg of 1-bromo-2-methylpropane were then added, and the mixture stirred another 3 hr until the starting material was down to 2% as measured by HPLC. The mixture was cooled to rt, and the solids were filtered off and rinsed with EtOAc (250 mL). The filtrate was then washed with saturated NH4Cl (2×200 mL), H2O (2×200 mL), and brine (100 mL), filtered through phase separation paper, and concentrated in vacuo to a yellow oil. Upon standing the oil crystallized, and was subsequently triturated with hexanes:EtOAc 20:1 (30 mL). The crystals were filtered and rinsed with hexanes (2×10 mL). Upon drying, 10.2 g of Compound #10 were obtained as an off-white, crystalline solid (84%). 1H NMR (300 MHz, CDCl3): δ 7.82 (m, 1H), 7.42-7.28 (m, 5H), 7.12 (d, 2H), 7.02 (t, 1H), 5.40 (s, 2H), 4.14 (d, 2H), 2.35 (sept, 1H), 0.98 (d, 6H) ppm. HPLC analysis (5:10:85 H2O:A1:MeOH) showed a purity of 98% with a retention time of 4.9 min and 2% starting material with a retention time of 3.4 min. Extension of the reaction time should reduce the percentage of starting material.

Workup

  1. customA 500 mL flask fitted with a stir-bar, addition funnel
  2. temperatureThe mixture was cooled to rt
  3. filtrationthe solids were filtered off
  4. washrinsed with EtOAc (250 mL)
  5. washThe filtrate was then washed with saturated NH4Cl (2×200 mL), H2O (2×200 mL), and brine (100 mL)
  6. filtrationfiltered through phase separation paper
  7. concentrationconcentrated in vacuo to a yellow oil
  8. customcrystallized
  9. customwas subsequently triturated with hexanes:EtOAc 20:1 (30 mL)
  10. filtrationThe crystals were filtered
  11. washrinsed with hexanes (2×10 mL)
  12. customUpon drying

Sources & evidence

ORD record
ord-23ba7a0dbb4e400eaba16ab90ea168ae
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

Loading…