Acetic Acid → Methyl 2-(4-(cyanomethyl)benzyl)-3-oxobutanoate

HRID 445051Notes

Reaction equation

HRID 445051 reaction equation
[OH:1][CH:2]([CH3:9])[C:3](=[CH2:8])[C:4]([O:6][CH3:7])=[O:5].Br[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]#[N:19])=[CH:13][CH:12]=1.C(N(CC)CC)C.C(O)(=O)C>C(#N)C.C1(C)C=CC=CC=1>[C:18]([CH2:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:8][CH:3]([C:2](=[O:1])[CH3:9])[C:4]([O:6][CH3:7])=[O:5])=[CH:12][CH:13]=1)#[N:19]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 27914Benzeneacetonitrile, 4-bromo-HCID 5080248Methyl 3-hydroxy-2-methylen-butanoat

Product 1

HCID 59590640Methyl 2-(4-(cyanomethyl)benzyl)-3-oxobutanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A stirred mixture of methyl 3-hydroxy-2-methylenebutanoate (30.0 g, 0.23 mol), 2-(4-bromophenyl)acetonitrile (54.2 g, 0.28 mol), PdCl2[P(o-tol)3]2 (1.8 g, 2 mmol) and triethylamine (46.7 g, 0.46 mol) in acetonitrile (90 g) was heated at 70° C. for 6 hours under a N2 atmosphere. The mixture was cooled to 25° C., diluted with toluene (300 g) and 10% aq. acetic acid (360 g), and stirred for 10 minutes. The organic layer was separated, washed with water (360 g), and concentrated under reduced pressure to give the subtitle compound as a red oil, 67.3 g. This product was used in the next step without further purification.

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. customThe organic layer was separated
  3. washwashed with water (360 g)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ff1ea654c3f24d7ab597a834cff93c9c
Source dataset
uspto-grants-2013_07
Patent number
US08476288B2

Reaction notes

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