Bromobenzene → HCID 50997393, compound

HRID 1404134Notes

Reaction equation

HRID 1404134 reaction equation
[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][C:5]1[C:13]2[C:12]([OH:14])=[CH:11][C:10]([F:15])=[CH:9][C:8]=2[N:7]([CH2:16][CH3:17])[CH:6]=1.Br[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Cu]I>[CH2:16]([N:7]1[C:8]2[C:13](=[C:12]([O:14][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:11]=[C:10]([F:15])[CH:9]=2)[C:5]([CH2:4][CH2:3][N:2]([CH3:1])[CH3:18])=[CH:6]1)[CH3:17]

Participants

6

Reactant 3

HCID 7961BromobenzeneHCID 11430Potassium CarbonateHCID 46868902HCID 46868902, compound

Product 1

HCID 50997393HCID 50997393, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-9b (80 mg, 0.32 mmol), bromobenzene (100 mg, 0.64 mmol), K2CO3 (110 mg, 0.8 mmol) and CuI (152 mg, 0.8 mmol) in 10 mL of dioxane was stirred at reflux overnight. After cooled to room temperature, the volatiles were evaporated under vacuum and the resulting residue was partitioned between water (10 mL) and ethyl acetate (10 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×15 mL). The organic layers were combined, washed with brine (2×30 mL), dried over MgSO4 and evaporated. The resulting brown residue was purified by preparative HPLC (acid condition, water/CH3CN, 25-30% CH3CN in 7.5 min, RT=6.5 min) to give 32-2 (3 mg, 3%) as a white solid. 1H-NMR (400 MHz, MeOD-d6): δ (ppm) 7.34 (t, J=8.0 Hz, 2H), 7.13-7.09 (m, 2H), 7.02 (d, J=8.0 Hz, 2H), 6.85 (d, J=11.2 Hz, 1H), 6.10 (d, J=11.2 Hz 1H), 4.05 (q, 2H), 3.33-3.28 (m, 2H), 3.11-3.07 (m, 2H), 2.74 (s, 6H), 1.33 (t, J=7.2 Hz, 3H). LRMS: calc 326.2 and found: 327.1 [M+1].

Workup

  1. temperatureat reflux overnight
  2. customthe volatiles were evaporated under vacuum
  3. customthe resulting residue was partitioned between water (10 mL) and ethyl acetate (10 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×15 mL)
  6. washwashed with brine (2×30 mL)
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe resulting brown residue was purified by preparative HPLC (acid condition, water/CH3CN, 25-30% CH3CN in 7.5 min, RT=6.5 min)

Sources & evidence

ORD record
ord-35a5ec3658b74e76a68d502b92f17f29
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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