2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → ethyl (2E,4E,6E)-6-fluoro-7-(4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-3-methyl-octa-2,4,6-trienoate

HRID 2180518Notes

Reaction equation

HRID 2180518 reaction equation
C(OP([CH2:9]/[C:10](/[CH3:17])=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.CN1CCCN(C)C1=O.C([Li])CCC.[F:32]/[C:33](=[C:36](/[C:38]1[CH:39]=[C:40]2[C:45](=[CH:46][C:47]=1[O:48][CH3:49])[O:44][C:43]([CH3:51])([CH3:50])[CH:42]=[C:41]2[CH:52]([CH3:54])[CH3:53])\[CH3:37])/[CH:34]=O>C1COCC1>[F:32]/[C:33](=[C:36](/[C:38]1[CH:39]=[C:40]2[C:45](=[CH:46][C:47]=1[O:48][CH3:49])[O:44][C:43]([CH3:51])([CH3:50])[CH:42]=[C:41]2[CH:52]([CH3:54])[CH3:53])\[CH3:37])/[CH:34]=[CH:9]/[C:10](/[CH3:17])=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

6

Reactant 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 6000084Ethyl 4-(diethoxyphosphoryl)-3-methylbut-2-enoateHCID 22490793(2E)-2-Fluoro-3-(4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-but-2-enal2×HCID 178418339Butyllithium

Product 1

HCID 86759708ethyl (2E,4E,6E)-6-fluoro-7-(4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-3-methyl-octa-2,4,6-trienoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 4-(diethoxyphosphoryl)-3-methyl-but-2E-enoate (240 mg, 0.91 mmol) in THF (10 mL), and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, 0.13 mL) under argon at −78° C. was slowly added n-butyl lithium (1.6 M in hexanes, 0.60 mL, 0.96 mmol). The resulting mixture was stirred at −78° C. for 15 min before a solution of (2E)-2-fluoro-3-(4-isopropyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-but-2-enal (Compound 95, 100 mg, 0.31 mmol) and THF (3 mL) was added via cannula. The resulting mixture was stirred at 0° C. for 1 h. The reaction was quenched with saturated NH4Cl, and the product was extracted with diethyl ether. The combined ethereal layers were washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 5% ethyl acetate in hexane) to yield the title compound as a yellow oil.

Workup

  1. customat −78° C.
  2. additionwas added via cannula
  3. customThe reaction was quenched with saturated NH4Cl
  4. extractionthe product was extracted with diethyl ether
  5. washThe combined ethereal layers were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (silica gel, 5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-590a600b01244160bc2b885ed27a2294
Source dataset
uspto-grants-2005_05
Patent number
US06887896B1

Reaction notes

Loading…