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

HRID 1159709Notes

Reaction equation

HRID 1159709 reaction equation
C([N-]C(C)C)(C)C.[Li+].Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][Br:15].[C:16]([O:21][CH2:22][CH3:23])(=[O:20])[CH:17]([CH3:19])[CH3:18]>C1COCC1>[CH2:22]([O:21][C:16](=[O:20])[C:17]([CH3:19])([CH3:18])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][Br:15])[CH3:23]

Participants

5

Reactant 3

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

Product 1

HCID 11265571Ethyl 7-bromo-2,2-dimethylheptanoateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under argon atmosphere and cooling with an ice-bath, a solution of lithium diisopropylamide in THF (1.7 L, 2.0 M, 3.4 mol) was slowly dropped into a solution of 1,5-dibromopentane (950 g, 4.0 mol) and ethyl isobutyrate (396 g, 3.4 mol) in THF (5 L) while keeping the temperature below +5° C. The reaction mixture was stirred at room temperature for 20 h and quenched by slow addition of saturated ammonium chloride solution (3 L). The resulting solution was divided into three 4-L portions. Each portion was diluted with saturated ammonium chloride solution (5 L) and extracted with ethyl acetate (2×2 L). Each 4-L portion of ethyl acetate was washed with saturated sodium chloride solution (2 L), 1 N hydrochloric acid (2 L), saturated sodium chloride solution (2 L), saturated sodium bicarbonate solution (2 L), and saturated sodium chloride solution (2 L). The three separate ethyl acetate layers were combined into a single 12-L portion, dried over magnesium sulfate, and concentrated in vacuo to give the crude material (1.7 L) which was purified by vacuum distillation. Two fractions were obtained: the first boiling at 88-104° C./0.6 torr (184.2 g), the second at 105-120° C./1.4 torr (409.6 g) for a total yield of 60%. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 4.11 (q, 2 H, J=7.2 Hz), 3.39 (t, 2 H, J=6.8 Hz), 1.85 (m, 2 H), 1.56-1.35 (m, 4 H), 1.24 (t, 3 H, J=7.2 Hz), 1.31-1.19 (m, 2 H), 1.16 (s, 6 H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 177.9, 60.2, 42.1, 40.5, 33.8, 32.6, 28.6, 25.2, 24.2, 14.3. HRMS (EI, pos): Calcd. for C11H22BrO2 (MH+): 265.0803, found: 265.0810.

Workup

  1. temperatureUnder argon atmosphere and cooling with an ice-bath
  2. customthe temperature below +5° C
  3. customquenched by slow addition of saturated ammonium chloride solution (3 L)
  4. additionEach portion was diluted with saturated ammonium chloride solution (5 L)
  5. extractionextracted with ethyl acetate (2×2 L)
  6. washEach 4-L portion of ethyl acetate was washed with saturated sodium chloride solution (2 L), 1 N hydrochloric acid (2 L), saturated sodium chloride solution (2 L), saturated sodium bicarbonate solution (2 L), and saturated sodium chloride solution (2 L)
  7. customThe three separate ethyl acetate layers
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-992ab06127f14a96b961c3aed6e6541f
Source dataset
uspto-grants-2010_10
Patent number
US07812199B2

Reaction notes

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