Acetic Acid → HCID 86664659, compound

HRID 1917426Notes

Reaction equation

HRID 1917426 reaction equation
[C:1]([CH:5]1[C@@:9]([CH2:13][CH2:14][CH2:15][O:16][Si](C(C)(C)C)(C)C)([C:10]([OH:12])=[O:11])[CH2:8][C:7](=[O:24])[N:6]1[C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:43]N1C(=O)CCC1=O.[Cl-].[NH4+].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C>[C:1]([CH:5]1[C@@:9]([CH2:13][CH2:14][CH2:15][OH:16])([C:10]([OH:12])=[O:11])[CH:8]([Cl:43])[C:7](=[O:24])[N:6]1[C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 311Citric AcidHCID 25517Ammonium ChlorideHCID 31398ChlorosuccinimideHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 86664660HCID 86664660, compound

Product 1

HCID 86664659HCID 86664659, compoundYield 63.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent2×

Procedure

Under nitrogen atmosphere, to a solution of tert-butyl (3S)-3-[3-(tert-butyldimethylsilyloxy)propan-1-yl]-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid (960 mg, 2.08 mmol) in THF (15 mL) was added 1.0M lithium bis(trimethylsilyl)amide in THF solution (2.29 mL, 2.29 mmol) at −78° C., and the mixture was stirred for 30 minutes. Then, N-chlorosuccinimide (333 mg, 2.50 mmol) added and the mixture was stirred for 1 hour at −60° C., and further stirred for 10 minutes at 0° C. To the mixture were added saturated aqueous solution of ammonium chloride and ethyl acetate. The separated organic layer was washed with water and brine. The solution was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. At 0° C., to a solution of this residue in THF (20 mL) were added acetic acid (0.24 mL, 4.16 mmol) and 1.0M tetrabutylammonium fluoride in THF solution (4.16 mL, 4.16 mmol), the mixture was stirred for 16 hours at room temperature. To the mixture were added 10% aqueous solution of citric acid and ethyl acetate. The separated organic layer was washed with water and brine. The solution was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (ethyl acetate/hexane=1:1→1:2) to afford 506 mg of the title compound as a pale yellow oil.

Workup

  1. stirringthe mixture was stirred for 1 hour at −60° C.
  2. stirringfurther stirred for 10 minutes at 0° C
  3. washThe separated organic layer was washed with water and brine
  4. dry with materialThe solution was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. stirringthe mixture was stirred for 16 hours at room temperature
  7. washThe separated organic layer was washed with water and brine
  8. dry with materialThe solution was dried over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe residue was purified by silica gel
  11. customflush column chromatography (ethyl acetate/hexane=1:1→1:2)

Sources & evidence

ORD record
ord-c5a11075ba494d578c9d8e457e65169d
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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