2-Bromo-2-methylpropionyl bromide → Methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

HRID 2353077Notes

Reaction equation

HRID 2353077 reaction equation
[C:1]1([C:7]23[CH2:14][CH2:13][C:10]([CH2:15][C:16]([O:18][CH3:19])=[O:17])([CH2:11][CH2:12]2)[CH2:9][CH2:8]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[Br:24][C:25]([CH3:30])([CH3:29])[C:26](Br)=[O:27]>C(Cl)Cl>[Br:24][C:25]([CH3:30])([CH3:29])[C:26]([C:4]1[CH:3]=[CH:2][C:1]([C:7]23[CH2:8][CH2:9][C:10]([CH2:15][C:16]([O:18][CH3:19])=[O:17])([CH2:13][CH2:14]2)[CH2:11][CH2:12]3)=[CH:6][CH:5]=1)=[O:27]

Participants

5

Reactant 3

HCID 886852-Bromo-2-methylpropionyl bromideHCID 6451240Aluminum(III) ChlorideHCID 25016427Methyl (4-phenylbicyclo[2.2.2]oct-1-yl)acetate2×

Product 1

HCID 25258107Methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice water cooled solution of crude methyl (4-phenylbicyclo[2.2.2]oct-1-yl)acetate (Intermediate 16; 961 mg, 3.53 mmol) in DCM (10 mL) was added aluminium chloride (1.4 g, 10.58 mmol) followed by the dropwise addition of 2-bromoisobutyryl bromide (0.45 mL, 3.53 mmol). The reaction mixture was allowed to stir at ˜0° C. for ˜40 mins, it was then poured onto ice-water (˜100 mL). The organic phase was separated and the aqueous phase washed with DCM (3×50 mL), the organic washings were combined, dried (MgSO4) and concentrated to leave a yellow gum. This was purified on a 120 g silicyle silica cartridge, loading in DCM and eluting with 0-10%-20% isohexane-EtOAc, the product eluting at 10% EtOAc. The mixed fractions were combined and recolumned on a 120 g silica cartridge as described above; to yield the title compound as a white solid, (705 mg 1.67 mmol, 47%). 1H NMR (CDCl3) δ 1.09 (d, 3H), 1.50-1.57 (m, 3H), 1.67-1.74 (m, 3H), 1.82-1.86 (m, 6H), 2.03 (s, 6H), 2.27 (q, 1H), 3.67 (s, 3H), 7.37 (d, 2H), 8.11 (d, 2H); GC-MS CI m/e MH+ 421.

Workup

  1. additionit was then poured onto ice-water (˜100 mL)
  2. customThe organic phase was separated
  3. washthe aqueous phase washed with DCM (3×50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto leave a yellow gum
  7. customThis was purified on a 120 g silicyle silica cartridge, loading in DCM
  8. washeluting with 0-10%-20% isohexane-EtOAc
  9. washthe product eluting at 10% EtOAc

Sources & evidence

ORD record
ord-97a89e0482af4bedb54e70c883d03c6d
Source dataset
uspto-grants-2010_07
Patent number
US07749997B2

Reaction notes

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