Acetic Acid → Methyl (E)-7-[1-butyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidin-6-yl]-5-hydroxy-3-oxo-hept-6-enoate

HRID 1885716Notes

Reaction equation

HRID 1885716 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[CH2:16]([N:20]1[C:25]2[N:26]=[C:27]([CH:41]([CH3:43])[CH3:42])[C:28](/[CH:37]=[CH:38]/[CH:39]=[O:40])=[C:29]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:24]=2[C:23](=[O:44])[NH:22][C:21]1=[O:45])[CH2:17][CH2:18][CH3:19].C(O)(=O)C>O1CCCC1.CCCCCC.O>[CH2:16]([N:20]1[C:25]2[N:26]=[C:27]([CH:41]([CH3:42])[CH3:43])[C:28](/[CH:37]=[CH:38]/[CH:39]([OH:40])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:29]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:24]=2[C:23](=[O:44])[NH:22][C:21]1=[O:45])[CH2:17][CH2:18][CH3:19]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 19980383(E)-3-[1-Butyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidin-6-yl]prop-2-enalHCID 178418339Butyllithium

Product 1

HCID 67836864Methyl (E)-7-[1-butyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidin-6-yl]-5-hydroxy-3-oxo-hept-6-enoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

0.7 g (6 mmol) of methyl acetoacetate are added dropwise at 0°-5° C. to a suspension of 0.2 g (6.6 mmol) of 80% strength sodium hydride in 8 ml of anhydrous tetrahydrofuran. After 15 min, 4.9 ml (8 mmol) of 15% strength butyllithium in hexane are added dropwise in the course of 10 min and the mixture is kept at 0° C. for a further 15 min. 0.82 g (2 mmol) of the compound from Example 6 and 10 ml of tetrahydrofuran are then added and the mixture is stirred at 0°-5° C. for 1 h. 1.2 g (20 mmol) of acetic acid in 20 ml of water are then added cautiously, the mixture is extracted three times with ethyl acetate, and the organic phase is washed with sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed on 40 g of 230-400 mesh silica gel (φ 3 cm) using petroleum/ethyl acetate (2:1) to (1:3).

Workup

  1. waitthe mixture is kept at 0° C. for a further 15 min
  2. extractionthe mixture is extracted three times with ethyl acetate
  3. washthe organic phase is washed with sodium chloride solution
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue is chromatographed on 40 g of 230-400 mesh silica gel (φ 3 cm)

Sources & evidence

ORD record
ord-96f4823ffc6b4347a5c470fd8325f760
Source dataset
uspto-grants-1992_09
Patent number
US05145959

Reaction notes

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