Dimethylformamide → (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone

HRID 1354540Notes

Reaction equation

HRID 1354540 reaction equation
[H-].[Na+].ClCCl.CN(C)C=O.[F:11][C:12]([F:32])([F:31])[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[CH2:21][C@@H:22](OS(C)(=O)=O)[CH2:23][CH3:24])=[CH:15][CH:14]=1>O>[CH2:23]([C@H:22]1[N:19]([C:16]2[CH:17]=[CH:18][C:13]([C:12]([F:32])([F:31])[F:11])=[CH:14][CH:15]=2)[C:20](=[O:30])[CH2:21]1)[CH3:24]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 6344Dichloromethane2×HCID 24758Sodium hydrideHCID 11961983(S)-N-[4-(trifluoromethyl)phenyl]-3-methanesulfonyloxypentanoic acid amide

Product 1

HCID 10105825(R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

158.7 mg of sodium hydride (60 wt %; 3.97 mmol) was suspended in a mixed solution of dichloromethane (2.7 mL) and dimethylformamide (10.8 mL) and to the solution, a mixed solution of 1,346.2 mg (3.97 mmol) of (S)-N-[4-(trifluoromethyl)phenyl]-3-methanesulfonyloxypentanoic acid amide produced in Example 3, dichloromethane (2.7 mL) and dimethylformamide (10.8 mL) was added dropwise at room temperature for 15 minutes. After stirring at room temperature for further 1 hour, water (25 mL) was added and extraction was carried out with ethyl acetate. The organic layer was washed with saturated brine and the product was dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure to obtain (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone as a brown solid (996.3 mg, crude yield: 87%). The optical purity of the product was determined by HPLC analysis (column; Daicel Chiral Pack AD-H 4.6×250 mm: eluent; hexane/isopropanol=95/5: flow rate; 1.0 mL/min: column temperature; 30° C.: detector; UV 210 nm: retention time; (S) antipode=7.6 minutes, (R) antipode=8.8 minutes) to be 83.0% ee. 1H-NMR (CDCl3, 400 MHz/ppm): δ 0.99 (3H, t), 1.63-1.73 (1H, m), 2.11-2.21 (1H, m), 2.79 (1H, dd), 3.23 (1H, dd), 4.07-4.13 (1H, m), 7.47 (2H, d), 7.58 (2H, d)

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialthe product was dried with anhydrous sodium sulfate
  4. customThe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-e1fbb22990364d50bc0044d13ba2afc2
Source dataset
uspto-grants-2007_05
Patent number
US07223859B2

Reaction notes

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