Allyl iodide → (3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl) phenyl]pyrrolidin-2-one

HRID 1972248Notes

Reaction equation

HRID 1972248 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH2:16][CH2:15][C:14]3=[O:28])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:41](I)[CH:42]=[CH2:43]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[CH:19]=4)[CH2:16][C@H:15]([CH2:43][CH:42]=[CH2:41])[C:14]3=[O:28])=[CH:9][CH:8]=2)=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 11166Allyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 59485681(R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one

Product 1

HCID 59485752(3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl) phenyl]pyrrolidin-2-oneYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (67 mg, 0.155 mmol) in THF (1 mL) is cooled to 0° C., then LiHMDS (0.31 mL, 1.0 M in THF, 0.31 mmol) is added. After addition, the resulting solution is further stirred at 0° C. for 45 min. Then allyl iodide (52 mg, 0.31 mmol) is added at 0° C. The resulting mixture is stirred at 0° C. for 1 h and 45 min, then the reaction is quenched with saturated NH4Cl solution (0.2 mL). THF is removed by evaporation and then the residue is dissolved in CH2Cl2 (40 mL), washed with brine (10 mL) and dried over Na2SO4. After concentration, the residue is purified on silica gel (0-50% ethyl acetate in hexane) to give (3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (58.5 mg, 80%) and its (3R)-diastereomer (6.5 mg, 9%) as a colorless oil. HPLC-MS calculated for C26H21ClF3NO2 (M+H+) 472.12, found 472.10.

Workup

  1. additionAfter addition
  2. stirringThe resulting mixture is stirred at 0° C. for 1 h and 45 min
  3. customthe reaction is quenched with saturated NH4Cl solution (0.2 mL)
  4. customTHF is removed by evaporation
  5. dissolutionthe residue is dissolved in CH2Cl2 (40 mL)
  6. washwashed with brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe residue is purified on silica gel (0-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-97b3bf98f9c848e7acf5467807b714a5
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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