Diisopropylamine → (E,E)-5,9,13-Trimethyl-4,8,12-tetradecatrienoic acid, 1,1-dimethylethyl ester

HRID 22202

Reaction equation

HRID 22202 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].CN(C)P(N(C)C)(N(C)C)=O.[CH3:32]/[C:33](/[CH2:37][CH2:38]/[CH:39]=[C:40](\[CH3:47])/[CH2:41][CH2:42][CH:43]=[C:44]([CH3:46])[CH3:45])=[CH:34]\[CH2:35]Br>O1CCCC1>[CH3:32]/[C:33](/[CH2:37][CH2:38]/[CH:39]=[C:40](\[CH3:47])/[CH2:41][CH2:42][CH:43]=[C:44]([CH3:46])[CH3:45])=[CH:34]\[CH2:35][CH2:14][C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 10908tert-Butyl acetateHCID 12679HexamethylphosphoramideHCID 5366048(2E,6E)-1-bromo-3,7,11-trimethyldodeca-2,6,10-trieneHCID 178418339Butyllithium

Product 1

HCID 11782198(E,E)-5,9,13-Trimethyl-4,8,12-tetradecatrienoic acid, 1,1-dimethylethyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 9.60 mL (68.5 mmol, 1.5 eq.) of diisopropylamine in 100 mL of tetrahydrofuran (THF) at -78° C. under argon was added 28.2 mL (45.0 mmol, 1.0 eq.) of 1.6M n-butyllithium in hexanes over 20 minutes. After warming to 0° C. for 15 minutes, the solution was recooled to -78° C. and 6.05 mL (45 mmol, 1.0 eq.) of t-butyl acetate was added over 20 minutes. After an additional 15 minutes, 16.0 mL (92 mmol, 2.05 eq.) of hexamethylphosphoramide (HMPA) was added, followed by a solution of 12.53 g (45.0 mmol) of Part A(1) farnesyl bromide in 100 mL of THF over 20 minutes. The reaction was stirred at -78° C. for 2.5 hours, quenched with saturated NH4Cl and allowed to warm to room temperature. After diluting with 400 mL of ethyl acetate, the mixture was washed with four 100 mL portions of water, and 200 mL of brine, dried over MgSO4 and evaporated to provide 12.96 g of crude product as a yellow oil. Purification by flash chromatography on 1 kg of silica gel, eluted with 1:9 ethyl acetate:petroleum ether afforded 9.39 g (65%) of title compound as a pale yellow oil.

Workup

  1. customwas recooled to -78° C.
  2. customquenched with saturated NH4Cl
  3. temperatureto warm to room temperature
  4. additionAfter diluting with 400 mL of ethyl acetate
  5. washthe mixture was washed with four 100 mL portions of water, and 200 mL of brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customto provide 12.96 g of crude product as a yellow oil
  9. customPurification by flash chromatography on 1 kg of silica gel
  10. washeluted with 1:9 ethyl acetate

Sources & evidence

ORD record
ord-77f2e4a11da042f9b3126b43ad87ffba
Source dataset
uspto-grants-1995_06
Patent number
US05428028

Linked notes

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