Acetic Acid → HCID 10994638, compound

HRID 1108482Notes

Reaction equation

HRID 1108482 reaction equation
[C:1]([O:4][CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:12]([NH2:15])[CH:13]=2)[N:8]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:7]1)(=[O:3])[CH3:2].[C:31]([O:36][CH3:37])(=[O:35])[C:32]([CH3:34])=O.C(O)(=O)C.O>C1C=CC=CC=1.CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:4][CH2:5][C@H:6]1[C:14]2=[C:13]3[C:12](=[C:11]([O:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:10]=[C:9]2[N:8]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:7]1)[NH:15][C:32]([C:31]([O:36][CH3:37])=[O:35])=[CH:34]3)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 11748Methyl pyruvateHCID 10916632HCID 10916632, compound

Product 1

HCID 10994638HCID 10994638, compoundYield 10.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 241BenzeneSolventHCID 31374DimethylacetamideSolvent

Procedure

1.24 g (3.0 mmole) of (3S)-3-acetoxymethyl-5-amino-6-benzyloxy-1-t-butoxycarbonylindoline, 0.46 g (4.5 mmole) of methyl pyruvate, and 0.2 ml of acetic acid were heated to reflux in 30 ml of benzene for 5 hours using a Dean-Stark apparatus (Chem.Pharm.Bull. 24,1273 (1976)). The reaction mixture was washed with 5% sodium bicarbonate aqueous solution, dried over anhydrous sodium sulfate, and filtrated. The obtained filtrate was concentrated to give a residue, to which 1.35 g (6.0 mmole) of palladium acetate was then added, and the resulting mixture was heated in 100 ml of dimethylacetamide at 90° C. for 1 hour. The obtained reaction mixture was poured into water, the resulting mixture was thrice extracted with toluene-hexane (5:1), the combined organic layer was dried over anhydrous sodium sulfate, and filtrated. The obtained filtrate was concentrated to give a residue, which was then purified by silica gel column chromatography with changing an eluate from hexane:ethyl acetate (3:1) to hexane:ethyl acetate (2.5:1) to give 0.15 g of methyl (1S)-1-acetoxymethyl-5-benzyloxy-3-t-butoxycarbonyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-7-carboxylate. Yield, 10%. This sample gave the same spectroscopic data as those obtained in Example 2.

Workup

  1. washThe reaction mixture was washed with 5% sodium bicarbonate aqueous solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltrated
  4. concentrationThe obtained filtrate was concentrated
  5. customto give a residue
  6. customThe obtained reaction mixture
  7. extractionextracted with toluene-hexane (5:1)
  8. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltrated
  10. concentrationThe obtained filtrate was concentrated
  11. customto give a residue, which
  12. customwas then purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d59a0ce42ec74b02b72f8a872b69611c
Source dataset
uspto-grants-2000_05
Patent number
US06066742

Reaction notes

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