Hydrochloric Acid → HCID 51041670, compound

HRID 338828Notes

Reaction equation

HRID 338828 reaction equation
C([C@@:4]1([CH3:19])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5]1)(=O)N.FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.Cl.C([O-])([O-])=O.[K+].[K+].[CH3:48][C:49]([O:52][C:53]([O:55]C(OC(C)(C)C)=O)=O)([CH3:51])[CH3:50].CC#[N:65].O>C(OCC)(=O)C.C1COCC1.CCOCC>[C:49]([O:52][C:53]([NH:65][C@@:4]1([CH3:19])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[CH2:5]1)=[O:55])([CH3:51])([CH3:50])[CH3:48]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 18373917Acetonitrile--water (1/1)HCID 86707398(S)-benzyl 3-carbamoyl-3-methylpyrrolidine-1-carboxylate

Product 1

HCID 51041670HCID 51041670, compoundYield 93.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (S)-Benzyl 3-carbamoyl-3-methylpyrrolidine-1-carboxylate (35.61 g, 135.8 mmol) in 1:1 MeCN/H2O (100 mL) was added [bis(trifluoroacetoxy)iodo]benzene (58.38 g, 135.8 mmol). The reaction mixture was stirred at ambient temperature for 2 hours and then at 86° C. (bath) for 2 hours. After cooling to ambient temperature, concentrated HCl (14.85 g, 407.3 mmol) and ether (200 mL) were added. The aqueous layer was separated and basified by K2CO3 (46.91 g, 339.4 mmol). To the resulting solution was added THF (150 mL) and Boc2O (37.04 g, 169.7 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. Ethyl acetate (100 mL) was added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (3:1 hexane/ethyl acetate) on silica gel to give (S)-benzyl 3-(tert-butoxycarbonylamino)-3-methylpyrrolidine-1-carboxylate (42.30 g, 126.5 mmol, 93.2% yield) as an oil.

Workup

  1. waitat 86° C. (bath) for 2 hours
  2. temperatureAfter cooling to ambient temperature
  3. customThe aqueous layer was separated
  4. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography (3:1 hexane/ethyl acetate) on silica gel

Sources & evidence

ORD record
ord-16b6a6cc7d384ba79e025a721ae94d5d
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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