Hydrochloric Acid → (5R)-1-Allyl-5-[4'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]-2-pyrrolidinone

HRID 28336Notes

Reaction equation

HRID 28336 reaction equation
CC([O-])(C)C.[K+].[CH2:7]([NH:10][C:11](=[O:33])[CH2:12][CH2:13][C@H:14](O)[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)[CH:8]=[CH2:9].S(Cl)(C1C=CC(C)=CC=1)(=O)=O.Cl>C1COCC1.O>[CH2:7]([N:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[CH2:13][CH2:12][C:11]1=[O:33])[CH:8]=[CH2:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 23665647Potassium tert-butoxideHCID 68928820(4S)-N-allyl-4-hydroxy-4-[4'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]butanamide

Product 1

HCID 68929317(5R)-1-Allyl-5-[4'-(trifluoromethoxy)-1,1'-biphenyl-4-yl]-2-pyrrolidinone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under argon, KOtBu (0.64 g, 5.7 mmol) is suspended, in a Schlenk tube which had been dried by heating, in THF (5 ml, anhydrous). At 0° C., a solution of (4S)-N-allyl-4-hydroxy-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide (XVI-1) (0.99 g, 2.6 mmol) in THF (8 ml, anhydrous) is added dropwise. The reaction mixture is stirred at 0° C. for 1 h and a solution of tosyl chloride (0.52 g, 2.7 mmol) in THF (5 ml, anhydrous) is then added dropwise over a period of 20 min. The mixture is stirred at 0° C. for 2 h and at room temperature for 16 h. For work-up, the mixture is admixed with water, adjusted to pH 5 using HCl and extracted with ethyl acetate. The combined organic phases are dried (Na2SO4) and concentrated. The residue (0.85 g, content: 81%, HPLC, 100% method) is further purified by flash chromatography (mobile phase: ethyl acetate/petroleum ether (40/60), 1:1).

Workup

  1. customwhich had been dried
  2. temperatureby heating, in THF (5 ml, anhydrous)
  3. stirringThe mixture is stirred at 0° C. for 2 h and at room temperature for 16 h
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic phases are dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue (0.85 g, content: 81%, HPLC, 100% method) is further purified by flash chromatography (mobile phase: ethyl acetate/petroleum ether (40/60), 1:1)

Sources & evidence

ORD record
ord-9e0209bcc32c4fab9b741c5b6e22d8bc
Source dataset
uspto-grants-2008_09
Patent number
US07419936B2

Reaction notes

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