Methanol → 3-(4-Fluorobenzyl)pyrrolidin-2-one

HRID 1744397Notes

Reaction equation

HRID 1744397 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH:6]=[C:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])=[CH:4][CH:3]=1.CO>[Ir].ClCCl>[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 540139903-(p-Fluorobenzylidene)-2-pyrrolidinone

Product 1

HCID 101490563-(4-Fluorobenzyl)pyrrolidin-2-oneYield 100%

Reagents, catalysts & solvents 2

HCID 23924IridiumCatalystHCID 6344DichloromethaneSolvent

Procedure

This example describes the preparation of I where n=1 and R1=p-fluorophenyl. In a nitrogen-filled glove box, a Fisher-Porter tube was charged with iridium catalyst prepared as in Example 1 (10 mg, 0.012 mmol) and 3-(p-fluorobenzylidene)-2-pyrrolidinone (250 mg, 1.3 mmol). Methanol (3 mL) and dichloromethane (3 mL) were added and the system was flushed 4 times with hydrogen and pressured to 60 psi (0.5 MPa) H2. After 18 h the reaction mixture was filtered through a short pad of silica. The solvent was removed at reduced pressure to afford 3-p-fluorobenzyl-2-pyrrolidinone (250 mg, 100%) as a white crystalline solid. Chiral HPLC analysis (Chiralpak OD, 95% heptane, 4.9% isopropanol, 0.05% trifluoroacetic acid, 0.05% n-hexylamine, 40° C.) indicated that conversion was 100% and the enantiomeric excess was 88%. 19F NMR δ −117.39; 13C NMR δ 26.92, 35.90, 40.44, 42.88, 115.44 (d, J=21 Hz), 130.58, 135.21, 161.77 (d, J=241 Hz), 179.72; 1H NMR: δ 1.83 (m, 1H), 2.15 (m, 1H), 2.66 (m, 2H), 3.11-3.32 (m. 3H), 6.47 (br s, 1H), 7.00 (m, 2H), 7.15 (m, 2H).

Workup

  1. customthe preparation of I where n=1 and R1=p-fluorophenyl
  2. additionIn a nitrogen-filled glove box
  3. customthe system was flushed 4 times with hydrogen
  4. filtrationAfter 18 h the reaction mixture was filtered through a short pad of silica
  5. customThe solvent was removed at reduced pressure

Sources & evidence

ORD record
ord-6fbceb7027604543b787d1dab1f7bd09
Source dataset
uspto-grants-2006_03
Patent number
US07015320B2

Reaction notes

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