Carbon tetrabromide → HCID 69173780, compound

HRID 1917427Notes

Reaction equation

HRID 1917427 reaction equation
C([CH:5]1[C@@:9]([CH2:13][CH2:14][CH2:15]O)([C:10]([OH:12])=[O:11])[CH:8]([Cl:17])[C:7](=[O:18])[N:6]1[C@@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])(C)(C)C.C(Br)(Br)(Br)Br.C1(P([C:45]2[CH:50]=[CH:49]C=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:51][Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+]>ClCCl.C1COCC1.C(OCC)(=O)C>[C:50]([O:12][C:10]([C@@:9]12[CH2:13][CH2:14][CH2:15][C@:8]1([Cl:17])[C:7](=[O:18])[N:6]([C@@H:19]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH3:20])[CH2:5]2)=[O:11])([CH3:49])([CH3:45])[CH3:51]

Participants

9

Reactant 5

HCID 11205Carbon tetrabromide3×HCID 11776Triphenylphosphine3×HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 86664659HCID 86664659, compound

Product 1

HCID 69173780HCID 69173780, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

At 0° C., to a solution of tert-butyl (3S)-4-chloro-3-(3-hydroxypropan-1-yl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid (500 mg, 1.31 mmol) in dichloromethane (10 mL) were added carbon tetrabromide (434 mg, 1.31 mmol) and triphenylphosphine (344 mg, 1.31 mmol). After stirring the mixture for 2 hours at room temperature, carbon tetrabromide (143 mg, 0.431 mmol) and triphenylphosphine (114 mg, 0.434 mmol) were added to the mixture. After stirring for 2 hours, carbon tetrabromide (72 mg, 0.216 mmol) and triphenylphosphine (57 mg, 0.217 mmol) were added and the mixture was stirred for 16 hours. The solvent was distilled off under reduced pressure. The residue was purified by short silica gel flush column chromatography (15% ethyl acetate/hexane) to afford a colorless oil. Under nitrogen atmosphere, to a solution of this oil in THF (12 mL) was added 1.0M lithium bis(trimethylsilyl)amide in THF solution (1.46 mL, 1.46 mmol) at −78° C., and the reaction mixture was warmed to 0° C. over 2 hours. To the mixture were added saturated aqueous solution of ammonium chloride and ethyl acetate. The separated organic layer was washed with water and brine. The solution was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (15% ethyl acetate/hexane) to afford 337 mg of the title compound as a pale yellow solid.

Workup

  1. stirringAfter stirring for 2 hours
  2. stirringthe mixture was stirred for 16 hours
  3. distillationThe solvent was distilled off under reduced pressure
  4. customThe residue was purified by short silica gel
  5. customflush column chromatography (15% ethyl acetate/hexane)
  6. customto afford a colorless oil
  7. temperaturethe reaction mixture was warmed to 0° C. over 2 hours
  8. washThe separated organic layer was washed with water and brine
  9. dry with materialThe solution was dried over anhydrous sodium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel
  12. customflush column chromatography (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9e7573b68fb44aaa998dbfc3196350f3
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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