tert-Butanol → tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate

HRID 17630Notes

Reaction equation

HRID 17630 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].C[C@:9]1([C:23](OC(C)(C)C)=O)[CH2:13][C:12](=[O:14])[N:11]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:10]1.C([N:32](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:54](O)([CH3:57])([CH3:56])[CH3:55]>ClCCl>[CH3:23][C@:9]1([NH:32][C:3](=[O:4])[O:5][C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:13][C:12](=[O:14])[N:11]([C@@H:15]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16])[CH2:10]1

Participants

7

Reactant 5

HCID 6386tert-ButanolHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 577587301,1-Dimethylethyl (3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]-3-pyrrolidinecarboxylate

Product 1

HCID 51041667tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamateYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

With cooling with ice, trifluoroacetic acid (7 ml) was added to a dichloromethane (14 ml) solution of tert-butyl (3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (I-342) (800 mg, 2.64 mmol), followed by stirring at room temperature for 13 hours. The reaction liquid was concentrated under reduced pressure, dissolved in chloroform, washed with saturated brine (60 ml). After drying over anhydrous sodium sulfate and concentration under reduced pressure, the resulting residue was dissolved in toluene (20 ml), then triethylamine (735 μl, 5.27 mmol) and diphenylphosphorylazide (739 μl, 3.43 mmol) were added, followed by stirring at room temperature for 30 minutes, then by stirring in an oil bath at 125° C. for 3 hours. tert-Butanol (20 ml) was added to the reaction liquid, followed by stirring in an oil bath at 100° C. for 11 hours. The reaction liquid was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, washed with saturated brine. After drying over anhydrous sodium sulfate and concentration, the resulting residue was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v) to obtain the entitled compound (500 mg, 60%) as a colorless oily substance.

Workup

  1. customThe reaction liquid
  2. concentrationwas concentrated under reduced pressure
  3. dissolutiondissolved in chloroform
  4. washwashed with saturated brine (60 ml)
  5. dry with materialAfter drying over anhydrous sodium sulfate and concentration under reduced pressure
  6. dissolutionthe resulting residue was dissolved in toluene (20 ml)
  7. stirringby stirring at room temperature for 30 minutes
  8. stirringby stirring in an oil bath at 125° C. for 3 hours
  9. stirringby stirring in an oil bath at 100° C. for 11 hours
  10. customThe reaction liquid
  11. concentrationwas concentrated under reduced pressure
  12. dissolutionthe residue was dissolved in ethyl acetate
  13. washwashed with saturated brine
  14. dry with materialAfter drying over anhydrous sodium sulfate and concentration
  15. customthe resulting residue was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v)

Sources & evidence

ORD record
ord-3f74e33b1ab04ca8875564b22ab39405
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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