Hydrochloric Acid → (1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917348Notes

Reaction equation

HRID 1917348 reaction equation
[C:1]([O:5][C:6]([C@@:8]1([CH2:22][CH2:23][C:24](OC)=[O:25])[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.Cl>O1CCCC1>[C:1]([O:5][C:6]([C@@:8]12[CH2:22][CH2:23][C:24](=[O:25])[C@@H:12]1[C:11](=[O:13])[N:10]([C@@H:14]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH3:15])[CH2:9]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 67490882HCID 67490882, compoundHCID 86590273LDA THF ethylbenzene heptane

Product 1

HCID 67490920(1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl esterYield 69.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3S)-3-(2-Methoxycarbonyl-1-ethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (35.0 g, 93.2 mmol) was dissolved in tetrahydrofuran (1 L). A 2 M lithium diisopropylamide/heptane/tetrahydrofuran/ethylbenzene solution (100 mL, 200 mmol) was added dropwise in a nitrogen atmosphere at an internal temperature of −69° C. over 30 minutes. After stirring at the same temperature for one hour, the reaction solution was poured into a 1N hydrochloric acid solution (2 L) in an ice bath, followed by extraction with ethyl acetate (2 L, 1 L). The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the precipitated solid was collected by filtration to give 22.2 g of the title compound as pale red crystals. The filtrate was further concentrated to give 2.88 g of the title compound as pale red crystals. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2.09 g of the title compound as colorless crystals.

Workup

  1. extractionfollowed by extraction with ethyl acetate (2 L, 1 L)
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-893b8d1533a44660b56d01a79bd77412
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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