Ethyl bromoacetate → 3-Acetyl-6-methyl-4-oxoheptanoic acid ethyl ester

HRID 220472

Reaction equation

HRID 220472 reaction equation
[CH3:1][CH:2]([CH3:10])[CH2:3][C:4](=[O:9])[CH2:5][C:6](=[O:8])[CH3:7].[H-].[Na+].[CH2:13]([O:15][C:16](=[O:19])[CH2:17]Br)[CH3:14]>O1CCCC1>[CH2:13]([O:15][C:16](=[O:19])[CH2:17][CH:5]([C:6](=[O:8])[CH3:7])[C:4](=[O:9])[CH2:3][CH:2]([CH3:10])[CH3:1])[CH3:14]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 763542,4-Heptanedione, 6-methyl-

Product 1

HCID 866416513-Acetyl-6-methyl-4-oxoheptanoic acid ethyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add a solution of 6-methylheptane-2,4-dione (5.0 g, 35.16 mmol) in tetrahydrofuran (50 mL) dropwise to a cooled suspension (0° C.) of sodium hydride (1.69 g, 42.2 mmol, 60% dispersion in oil) in tetrahydrofuran (50 mL). After 1 hr., add bromoacetic acid ethyl ester (4.28 mL, 38.68 mmol) dropwise and stir at 0° C. to room temperature over 88 hr. Partition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL). Separate the organic layer, dry (sodium sulfate), filter and concentrate. Purify using silica gel chromatography (95:5 hexanes:ethyl acetate) to give 3-acetyl-6-methyl-4-oxoheptanoic acid ethyl ester (5.81 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 4.10 (m, 4H), 2.81 (d, 2H), 2.41 (t, 1H), 2.22 (s, 3H), 1.23 (m, 4H), 0.92 (m, 6H).

Workup

  1. customPartition the reaction mixture between ethyl acetate (200 mL) and saturated aqueous ammonium chloride solution (100 mL)
  2. customSeparate the organic layer
  3. dry with materialdry (sodium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify

Sources & evidence

ORD record
ord-a89542bd527947c79ea97fb83ad6b93d
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Linked notes

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