Hydrochloric Acid → ethyl 4-methyl-3-oxohexanoate

HRID 2423435Notes

Reaction equation

HRID 2423435 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.N1C=C[CH:13]=[CH:12][C:11]=1[C:16]1C=CC=CN=1.C([Li])CCC.CC(CC)C(Cl)=O.Cl>O1CCCC1>[CH3:16][CH:11]([CH2:12][CH3:13])[C:3](=[O:5])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14742,2'-BipyridineHCID 93697Butanoyl chloride, 2-methyl-HCID 3595298Propanedioic acid, monoethyl esterHCID 178418339Butyllithium

Product 1

HCID 13250489ethyl 4-methyl-3-oxohexanoateYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of monoethyl malonate (49.5 mL, 0.42 mol) and a few milligrams of 2,2′-bipyridyl in tetrahydrofuran at −70° C. was added 2.5 M n-butyl lithium in hexanes (0.34 L, 0.84 mol) dropwise over approximately 1.5 hours. Then 2-methylbutyryl chloride (26 mL, 0.21 mol) was added dropwise. The mixture was allowed to warm to ambient temperature and was then poured into 1 N hydrochloric acid. The mixture was extracted three times with ether and the combined organic layers were dried over magnesium sulfate and concentrated. The resulting oil was purified by vacuum distillation (boiling range 75-85° C.) to afford ethyl 4-methyl-3-oxohexanoate (36.4 g, 100%). 1H-NMR (400 MHz, DMSO-d6) δ 4.06 (q, J=7 Hz, 2H), 3.60 (s, 2H), 2.57-2.49 (m, 1H), 1.64-1.53 (m, 1H), 1.36-1.26 (m, 1H), 1.15 (t, J=7 Hz, 3H), 0.97 (d, J=7 Hz, 3H), 0.78 (t, J=7 Hz, 3H).

Workup

  1. extractionThe mixture was extracted three times with ether
  2. dry with materialthe combined organic layers were dried over magnesium sulfate
  3. concentrationconcentrated
  4. distillationThe resulting oil was purified by vacuum distillation (boiling range 75-85° C.)

Sources & evidence

ORD record
ord-1150763cdd5c4f57ae000eb4fa41503c
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

Loading…