Methanol → HCID 22229145, compound

HRID 1744398Notes

Reaction equation

HRID 1744398 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH:6]=[C:7]2[CH2:14][CH2:13][CH2:12][NH:11][C:9](=[O:10])[CH2:8]2)=[CH:4][CH:3]=1.CO>[Ir].ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[CH2:14][CH2:13][CH2:12][NH:11][C:9](=[O:10])[CH2:8]2)=[CH:15][CH:16]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 69554788HCID 69554788, compound

Product 1

HCID 22229145HCID 22229145, compoundYield 94.5%

Reagents, catalysts & solvents 2

HCID 23924IridiumCatalystHCID 6344DichloromethaneSolvent

Procedure

This example describes the preparation of I where n=3 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)caprolactam (250 mg, 1.1 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)caprolactam (230 mg, 92%) as a white crystalline solid. Chiral HPLC analysis (Chiralpak AS, 60% heptane, 39.2% isopropanol, 0.4% trifluoroacetic acid, 0.4% n-hexylamine, 40° C.) indicated that conversion was 100% and the enantiomeric excess was 67%. 19F NMR δ −117.99; 13C NMR δ 28.93, 29.47, 29.94, 36.73, 42.28, 45.65, 115.18 (d, J=21 Hz), 130.81, 136.47, 161.49 (d, J=241 Hz), 179.79; 1H NMR: δ 1.43 (m, 3H), 1.70 (m, 1H), 1.76 (m, 1H), 1.91 (m, 1H), 2.54 (app. dd, 1H), 2.67 (m, 1H), 3.12-3.31 (m, 3H), 6.78 (br s, 1H), 6.96 (m, 2H), 7.14 (m, 2H).

Workup

  1. customthe preparation of I where n=3 and R1=p-fluorophenyl
  2. additionIn a nitrogen-filled glove box
  3. customthe system was flushed 4 times with hydrogen and pressured to 60 psi (0.5 MPa) H2
  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-54945baa16d74d6985ca9715a4625fa0
Source dataset
uspto-grants-2006_03
Patent number
US07015320B2

Reaction notes

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