Acetic Acid → (3S)-3-(2-Hydroxyethyl)-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

HRID 1917308Notes

Reaction equation

HRID 1917308 reaction equation
[C:1]([O:5][C:6]([C@@:8]1([CH2:23][CH2:24][O:25][Si](C(C)(C)C)(C)C)[CH:12]([CH3:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>O1CCCC1.[Cl-].[Na+].O>[C:1]([O:5][C:6]([C@@:8]1([CH2:23][CH2:24][OH:25])[CH:12]([CH3:13])[C:11](=[O:14])[N:10]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 67490916HCID 67490916, compound

Product 1

HCID 67490980(3S)-3-(2-Hydroxyethyl)-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

The aforementioned crude (3S)-3-[2-(tert-butyldimethylsilyloxy)ethyl]-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester was dissolved in tetrahydrofuran (10 mL). Then, acetic acid (0.572 mL, 10.0 mmol) and a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (10.0 mL, 10.0 mmol) were sequentially added in a nitrogen atmosphere. After stirring at room temperature for 12 hours, the reaction solution was poured into a mixture of ethyl acetate (100 mL) and brine (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL), and then dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:2) to give 1.56 g (90%, two steps) of the diastereomer mixture title compound as a colorless oil.

Workup

  1. extractionfollowed by extraction with ethyl acetate (200 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was then concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:2)

Sources & evidence

ORD record
ord-dfcf47c24bb04c1385a395354843e18c
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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