HCID 2773818, compound → HCID 72647293, compound

HRID 1883226Notes

Reaction equation

HRID 1883226 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]([CH3:16])[CH2:7]P(OCC)(OCC)=O)[CH3:2].[Li]CCCC.[CH:23]([C:26]1[C:27]([O:41][CH2:42][CH2:43][CH3:44])=[C:28]([C:35]([CH2:39][CH3:40])=[CH:36][CH:37]=O)[CH:29]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:31]=1)([CH3:25])[CH3:24]>CN1CCCN(C)C1=O.C1COCC1>[CH2:1]([O:3][C:4](=[O:17])[CH:5]=[C:6]([CH3:16])[CH:7]=[CH:37][CH:36]=[C:35]([C:28]1[CH:29]=[C:30]([CH:32]([CH3:33])[CH3:34])[CH:31]=[C:26]([CH:23]([CH3:25])[CH3:24])[C:27]=1[O:41][CH2:42][CH2:43][CH3:44])[CH2:39][CH3:40])[CH3:2]

Participants

6

Reactant 3

HCID 2773818HCID 2773818, compoundHCID 85435439HCID 85435439, compound2×HCID 178418339Butyllithium

Product 1

HCID 72647293HCID 72647293, compoundYield 95.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

To a solution of 4-(diethoxy-phosphoryl)-3-methyl-but-2-enoic acid ethyl ester (10.6 mL, 43.6 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, 20 mL) and THF (80 mL) at −78° C. was added n-BuLi dropwise (1.6 M in hexanes, 27.2 mL, 43.6 mmol). After 10 min, 3-(3,5-diisopropyl-2-propoxy-phenyl)-pent-2-enal (Intermediate 6, 8.77 g, 29.0 mmol) in THF (15 mL and 5 mL rinse) was added slowly to the reaction. The mixture was stirred at −78° C. for 2h, was quenched with saturated NH4Cl and extracted with EtOAc. The organic layer was separated, washed successively with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2.5% EtOAc-hexanes) to yield the title compound as a yellow syrup (11.4 g, 95%).

Workup

  1. customwas quenched with saturated NH4Cl
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed successively with H2O, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (2.5% EtOAc-hexanes)

Sources & evidence

ORD record
ord-1f2717c195394dacba21282c35cc6e09
Source dataset
uspto-grants-2004_07
Patent number
US06759546B1

Reaction notes

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