Methyl acetoacetate → Methyl 3-oxo-5-(2-{[3-(tritylamino)propoxy]methyl}phenyl)pentanoate

HRID 481004Notes

Reaction equation

HRID 481004 reaction equation
[H-].[Na+].[C:3]([O:9][CH3:10])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].C([Li])CCC.Br[CH2:17][C:18]1[CH:48]=[CH:47][CH:46]=[CH:45][C:19]=1[CH2:20][O:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[O:6]=[C:5]([CH2:7][CH2:17][C:18]1[CH:48]=[CH:47][CH:46]=[CH:45][C:19]=1[CH2:20][O:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH2:4][C:3]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 18765879HCID 18765879, compoundHCID 178418339Butyllithium

Product 1

HCID 18765931Methyl 3-oxo-5-(2-{[3-(tritylamino)propoxy]methyl}phenyl)pentanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (448 mg/l 1.2 mmol) in THF (22 ml) was added a solution of methyl acetoacetate (1.30 g/11.2 mmol) in THF (4.5 ml) dropwise at 0° C. over 15 minutes. After 20 minutes at 0° C., n-butyl lithium (7,3 ml/11.2 mmol) was added dropwise at 0° C. over 15 minutes. After 20 minutes at 0° C., a solution of 3-{[2-(bromomethyl)benzyl]oxy}-N-trityl-1-propanamine in THF (6.6 ml) was added dropwise at 0° C., and the solution was stirred at 0° C. for 3 hours. The mixture was quenched with water, and the whole was extracted with ethyl acetate (100 ml×2). The combined organic layer was washed with brine (30 ml), dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in diethylether (100 ml) and hexane (100 ml). The solution was washed with water (50 ml×5), brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography (SiO2, 200-350 mesh/hexane:ethyl acetate=10:0-3:1) to afford a colorless oil (3.70 g/74%).

Workup

  1. waitAfter 20 minutes at 0° C.
  2. customThe mixture was quenched with water
  3. extractionthe whole was extracted with ethyl acetate (100 ml×2)
  4. washThe combined organic layer was washed with brine (30 ml)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in diethylether (100 ml)
  9. washThe solution was washed with water (50 ml×5), brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography (SiO2, 200-350 mesh/hexane:ethyl acetate=10:0-3:1)
  14. customto afford a colorless oil (3.70 g/74%)

Sources & evidence

ORD record
ord-9c4c9cfd709644a9944163dd1604acb4
Source dataset
uspto-grants-2003_11
Patent number
US06653313B2

Reaction notes

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