Methyl acetoacetate → Methyl 3-oxo-7,11,15-trimethylhexadeca-6,10,14-trienoate

HRID 488150Notes

Reaction equation

HRID 488150 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[CH2:11](Br)[CH:12]=[C:13]([CH2:15][CH2:16][CH:17]=[C:18]([CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH3:19])[CH3:14]>C1COCC1.CCCCCC>[O:4]=[C:3]([CH2:5][CH2:11][CH:12]=[C:13]([CH3:14])[CH2:15][CH2:16][CH:17]=[C:18]([CH3:19])[CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH2:2][C:1]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 3

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 550199Farnesyl bromide

Product 1

HCID 54245426Methyl 3-oxo-7,11,15-trimethylhexadeca-6,10,14-trienoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

Methyl acetoacetate (225 μL, 2.1 mmol) was added dropwise to a stirred suspension of sodium hydride (50% oil suspension, prewashed with hexane) (100 mg, 2.1 mmol) in anhydrous THF (5 mL) at 0° C. under an Argon atmosphere. The resulting solution was stirred 15 minutes at 0° C. and then treated with a 1.6 M solution (1.3 mL, 2.1 mmol) of n-butylithium in hexane over 2 minutes. The yellow solution was stirred 15 min at 0° C. and then treated dropwise with farnesyl bromide (545 KL, 2.0 mmol). The cloudy orange solution was stirred at 20° C. for 1 1/2 hours and then quenched by dropwise addition of saturated aqueous NH4Cl solution. The resulting mixture was diluted with ethyl acetate and washed with water, dried, filtered and evaporated to give the crude product which was used in the next step without purification. Diagnostic peaks in the NMR (300 MHz, CDCl3): δ 1.600 (6H, s), 1.614 (3H,s), 1.68 (3H, s), 1.9-2.1 (8H, m), 2.2-2.33 (2H, m), 2.58 (2H, t, J=6Hz), 3.448 (2H, s), 3.740 (3H,s), 5.05-5.15 (3H, m).

Workup

  1. stirringThe yellow solution was stirred 15 min at 0° C.
  2. stirringThe cloudy orange solution was stirred at 20° C. for 1 1/2 hours
  3. customquenched by dropwise addition of saturated aqueous NH4Cl solution
  4. additionThe resulting mixture was diluted with ethyl acetate
  5. washwashed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-c4cc71eca287494a942d7e06598499c1
Source dataset
uspto-grants-1994_03
Patent number
US05298655

Reaction notes

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