Water → (+/-)-5-[(1S*)(5-(N-phenylcarbamoyl)(2-thienyl))hydroxymethyl](4R*,5R*)-1-methyl-4-phenylpyrrolidin-2-one

HRID 1837989Notes

Reaction equation

HRID 1837989 reaction equation
Br[C:2]1[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]2[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.CC[N:24]([CH2:27][CH3:28])[CH2:25]C.N[C:30]1C=C[CH:33]=[CH:32][CH:31]=1.[OH2:36]>CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:27]1([NH:24][C:25]([C:2]2[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]3[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:4][CH:3]=2)=[O:36])[CH:28]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6115AnilineHCID 8471TriethylamineHCID 69891005(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one

Product 1

HCID 86587928(+/-)-5-[(1S*)(5-(N-phenylcarbamoyl)(2-thienyl))hydroxymethyl](4R*,5R*)-1-methyl-4-phenylpyrrolidin-2-oneYield 18%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one (200 mg, 0.55 mmol) in DMSO (20 mL) was added Et3N (166 mg, 1.64 mmol, 3 equiv), followed by dppf (23 mg, 0.05 mmol, 0.1 equiv), aniline (508 mg, 5.5 mmol, 10 equiv) and palladium(II) acetate (12 mg, 0.05 mmol, 0.1 equiv). The reaction mixture was heated to 80° C. under a CO atmosphere (1 Atm) overnight. The resulting mixture was treated with water (100 mL) and extracted with CH2Cl2 (100 mL). The organic layer was washed with a 1N HCl solution (100 mL) and a saturated NaCl solution (100 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was triturated (CH2Cl2) to give (±)-5-[(1S*)(5-(N-phenylcarbamoyl)(2-thienyl))hydroxymethyl](4R*,5R*)-1-methyl-4-phenylpyrrolidin-2-one (41 mg, 18%) as a white solid: mp 223-227° C.; TLC (80% EtOAc/hex) Rf 0.26; HPLC ES-MS m/z (rel abundance) 407 (MH+, 100%).

Workup

  1. extractionextracted with CH2Cl2 (100 mL)
  2. washThe organic layer was washed with a 1N HCl solution (100 mL)
  3. dry with materiala saturated NaCl solution (100 mL), dried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was triturated (CH2Cl2)

Sources & evidence

ORD record
ord-de897e9ad61d44c2ac6515edec834809
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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