Ethyl isobutyrate → Ethyl 7-bromo-2,2-dimethylheptanoate

HRID 873291Notes

Reaction equation

HRID 873291 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][Br:7].[C:8]([O:13][CH2:14][CH3:15])(=[O:12])[CH:9]([CH3:11])[CH3:10].[Li+].CC([N-]C(C)C)C>C1COCC1>[Br:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:9]([CH3:11])([CH3:10])[C:8]([O:13][CH2:14][CH3:15])=[O:12]

Participants

5

Reactant 3

HCID 7342Ethyl isobutyrateHCID 81001,5-DibromopentaneHCID 2724682Lithium diisopropylamide

Product 1

HCID 11265571Ethyl 7-bromo-2,2-dimethylheptanoateYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under argon atmosphere, a solution of 1,5-dibromopentane (500 g, 2.2 mol) and ethyl isobutyrate (221 g, 1.9 mol) in anhydrous THF (4 L) was chilled in a dry ice/acetone bath to −78° C. Over a 40 min period, LDA solution in THF (1.8 M, 1 L, 1.8 mol) was added dropwise. After the addition, the solution was allowed to stir overnight and gradually warm to room temperature. Careful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L) furnished a two-phase mixture. The organic layer was separated and evaporated under vacuum to a minimum volume (ca. 1 L). The organic residue was recombined with the aqueous layer and the resulting mixture was extracted with ethyl acetate (3×1 L). The combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L) before drying over anhydrous MgSO4. Concentration in vacuo gave crude material (468.7 g), which was then purified by distillation affording 205g (208.7 g, 44%) as a colorless oil. Bp 106-108° C./0.01 mm Hg. 1H NMR (CDCl3): δ 4.11 (q, 2H, J=7.2), 3.39 (t, 2H, J=6.8), 1.85 (m, 2H), 1.56-1.35 (m, 4H), 1.24 (t, 3H, J=7.2), 1.31-1.19 (m, 2H), 1.16 (s, 6H). 13C NMR (CDCl3): δ 177.9, 60.2, 42.1, 40.5, 33.8, 32.6, 28.6, 25.2, 24.2, 14.3. HRMS (EI): Calcd for C11H22BrO2 (MH1) 265.0803, found 265.0810.

Workup

  1. additionAfter the addition
  2. customCareful quenching of the excess base by slow addition of saturated aqueous NH4Cl solution (3 L)
  3. customfurnished a two-phase mixture
  4. customThe organic layer was separated
  5. customevaporated under vacuum to a minimum volume (ca. 1 L)
  6. extractionthe resulting mixture was extracted with ethyl acetate (3×1 L)
  7. washThe combined ethyl acetate layers were then washed with 1 N HCl (5 L), water (3 L) and saturated aqueous NaHCO3 solution (4 L)
  8. dry with materialbefore drying over anhydrous MgSO4
  9. concentrationConcentration in vacuo
  10. customgave crude material (468.7 g), which
  11. distillationwas then purified by distillation

Sources & evidence

ORD record
ord-edbcde4abc644a09b4abc01ae492ac05
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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