Water → 1-Butyl-5-(4-fluorophenyl)-6-hydroxymethyl-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidine

HRID 1885714Notes

Reaction equation

HRID 1885714 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH2:11]([N:15]1[C:20]2[N:21]=[C:22]([CH:37]([CH3:39])[CH3:38])[C:23]([C:32](OCC)=[O:33])=[C:24]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:19]=2[C:18](=[O:40])[NH:17][C:16]1=[O:41])[CH2:12][CH2:13][CH3:14].[H-].C([Al+]CCCC)CCC.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:11]([N:15]1[C:20]2[N:21]=[C:22]([CH:37]([CH3:38])[CH3:39])[C:23]([CH2:32][OH:33])=[C:24]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:19]=2[C:18](=[O:40])[NH:17][C:16]1=[O:41])[CH2:12][CH2:13][CH3:14]

Participants

7

Reactant 4

HCID 962WaterHCID 198796871-Butyl-6-ethoxycarbonyl-5-(4-fluorophenyl)-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidineHCID 21225700DiisobutylaluminumhydrideHCID 21879971Dibutylaluminium hydride

Product 1

HCID 198796961-Butyl-5-(4-fluorophenyl)-6-hydroxymethyl-7-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido(2,3-d)pyrimidine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

135 ml of a 1 molar solution of diisobutylaluminum hydride in toluene are slowly added under argon to a suspension of 19.2 g (45 mmol) of the compound from Example 3 in 400 ml of toluene at -75° C., which leads to a clear solution. After 1 hour, a further 30 ml of dibutylaluminum hydride solution are added at the same temperature, the mixture is stirred for a further hour and then allowed to warm to room temperature, 400 ml of water and 200 ml of ethyl acetate being added cautiously from -30° C. The mixture is filtered off with suction through kieselguhr and subsequently washed with ethyl acetate. After phase separation, the aqueous phase is extracted with ethyl acetate, and the combined organic phases are washed with sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. The residue is chromatographed in a column (φ 6 cm) on 500 g of 230-400 mesh silica gel using petroleum ether/ethyl acetate (2:1).

Workup

  1. filtrationThe mixture is filtered off with suction through kieselguhr
  2. washsubsequently washed with ethyl acetate
  3. customAfter phase separation
  4. extractionthe aqueous phase is extracted with ethyl acetate
  5. washthe combined organic phases are washed with sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue is chromatographed in a column (φ 6 cm) on 500 g of 230-400 mesh silica gel

Sources & evidence

ORD record
ord-226a5bb4abdb4398b650089c15febf8e
Source dataset
uspto-grants-1992_09
Patent number
US05145959

Reaction notes

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