Allyl bromide → HCID 58237168, compound

HRID 471886Notes

Reaction equation

HRID 471886 reaction equation
[Li]CCCC.C(N[CH:10]([CH3:12])[CH3:11])(C)C.CN1CCCN(C)C1=O.[CH3:22][O:23][C:24]([CH:26]1[CH2:35][CH:34]([C:36]([O:38][CH3:39])=[O:37])[CH2:33][C:28]2([O:32][CH2:31][CH2:30][O:29]2)[CH2:27]1)=[O:25].C(Br)C=C>C1COCC1.CCCCCC>[CH3:39][O:38][C:36]([C:34]1([CH2:12][CH:10]=[CH2:11])[CH2:35][CH:26]([C:24]([O:23][CH3:22])=[O:25])[CH2:27][C:28]2([O:29][CH2:30][CH2:31][O:32]2)[CH2:33]1)=[O:37]

Participants

8

Reactant 5

HCID 7841Allyl bromideHCID 7912DiisopropylamineHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 57485780HCID 57485780, compoundHCID 178418339Butyllithium

Product 1

HCID 58237168HCID 58237168, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

A 1.6 M hexane solution of n-BuLi (101 mL, 161 mmol) was added to the stirred anhydrous THF (300 mL) at −78° C., followed by diisopropylamine (16.2 g, 161 mmol). The reaction mixture was stirred at −78° C. for 15 min and at 0° C. for 1 h. The mixture was re-cooled to −78° C., 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPO) (48 g, 372 mmol) was added slowly, and the resultant white suspension was stirred for 30 min. A solution of 1,4-dioxaspiro[4.5]decane-7,9-dicarboxylic acid dimethyl ester (32 g, 124 mmol) in THF (100 mL) was added, the light yellowish solution was stirred for 30 min, then allyl bromide (16.6 g, 137 mmol) was added, the reaction mixture was allowed to warm to room temperature and left stirring at room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate; the organic extracts were combined and washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give 40 g of crude product as viscous oil. Purification by flash column chromatography on silica gel (hexane-chloroform-ethyl acetate 8:1:1) gave 23.8 g (65%) of the title compound, 1-allyl-5,5-difluoro-cyclohexane-1,3-dicarboxylic acid dimethyl ester as colorless oil. 1H NMR (400 MHz, CDCl3), δ: 5.7-5.6 (m, 1H), 5.10-5.00 (m, 2H), 4.0-3.8 (m, 4H), 3.68 (s, 6H), 3.08-2.98 (m, 1H), 2.5-2.3 (m, 2H), 2.15-2.08 (m, 1H), 1.98-1.92 (m, 1H), 1.65-1.58 (m, 1H), 1.45-1.38 (m, 1H), 1.28-1.18 (m, 1H). ES MS: 299.2 (M+1)+.

Workup

  1. temperatureThe mixture was re-cooled to −78° C.
  2. stirringthe resultant white suspension was stirred for 30 min
  3. stirringthe light yellowish solution was stirred for 30 min
  4. temperatureto warm to room temperature
  5. waitleft
  6. stirringstirring at room temperature overnight
  7. customThe reaction was quenched with saturated aqueous NH4Cl solution
  8. extractionextracted with ethyl acetate
  9. washwashed with water, brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customto give 40 g of crude product as viscous oil
  13. customPurification by flash column chromatography on silica gel (hexane-chloroform-ethyl acetate 8:1:1)

Sources & evidence

ORD record
ord-667c35af757f46e3bba39484b27b6104
Source dataset
uspto-grants-2014_01
Patent number
US08633190B2

Reaction notes

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