Ammonia → (3S,4S)-1-Benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-ethylpyrrolidine

HRID 1010556Notes

Reaction equation

HRID 1010556 reaction equation
C[Li].[CH2:3]([O:10][C:11]([N:13]1[CH2:17][C@H:16](COS(C2C=CC(C)=CC=2)(=O)=O)[C@H:15]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:14]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[NH4+].N.[CH2:41](OCC)[CH3:42]>[Cu]I.O>[CH2:3]([O:10][C:11]([N:13]1[CH2:17][C@H:16]([CH2:41][CH3:42])[C@H:15]([NH:30][C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:14]1)=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 3283Diethyl Ether2×HCID 25517Ammonium ChlorideHCID 86618513(3S,4S)-1-Benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-(p-toluenesulfonyloxy)methylpyrrolidineHCID 178418348HCID 178418348, compound

Product 1

HCID 59665274(3S,4S)-1-Benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-ethylpyrrolidine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

Under cooling with ice, a solution of methyllithium (121 mL, 1.02 M, diethyl ether solution) was added to a suspension of copper(I) iodide (11.8 g, 62.1 mmol) in diethyl ether (200 mL), followed by stirring for 30 minutes. The temperature of the reaction mixture was cooled to −78° C. A solution of (3S,4S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-(p-toluenesulfonyloxy)methylpyrrolidine (6.27 g, 12.4 mmol) in diethyl ether (140 mL) was added thereto. The temperature of the mixture was elevated gradually, followed by stirring for 1 hour under cooling with ice. Under cooling with ice, a saturated aqueous ammonium chloride solution (100 mL) and 28% aqueous ammonia (25 mL) were added to the resultant mixture, and then water (100 mL) was added thereto, followed by extraction with ethyl acetate (300 mL×2). The combined organic layer was washed by saturated brine (100 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure. The residue was purified through silica gel column chromatography (ethyl acetate:n-hexane=1:3 to 1:2), to thereby yield the title compound as a colorless oily substance (3.09 g, 71%).

Workup

  1. temperatureUnder cooling with ice
  2. stirringby stirring for 1 hour
  3. temperatureunder cooling with ice
  4. temperatureUnder cooling with ice
  5. extractionfollowed by extraction with ethyl acetate (300 mL×2)
  6. washThe combined organic layer was washed by saturated brine (100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified through silica gel column chromatography (ethyl acetate:n-hexane=1:3 to 1:2)

Sources & evidence

ORD record
ord-238fb56c2c2243d5890eb4c302c06310
Source dataset
uspto-grants-2011_07
Patent number
US07977327B2

Reaction notes

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