Lithium diisopropylamide → HCID 19430447, compound

HRID 1078039Notes

Reaction equation

HRID 1078039 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([I:22])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]([C:10](=[O:12])[CH3:11])=[C:8]([CH2:13][CH3:14])[N:7]=[C:6]1[CH2:15][CH2:16][CH3:17].C([N-]C(C)C)(C)C.[Li+].[O:31]([C:38]1[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=1[CH2:40]I)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[F:1][C:2]1[CH:21]=[C:20]([I:22])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]([C:10]([CH2:11][CH2:40][C:39]2[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=2[O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:12])=[C:8]([CH2:13][CH3:14])[N:7]=[C:6]1[CH2:15][CH2:16][CH3:17]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 19430452HCID 19430452, compoundHCID 19430463HCID 19430463, compound

Product 1

HCID 19430447HCID 19430447, compoundYield 29.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

1-(2-fluoro-4-iodobenzyl)-5-acetyl-4-ethyl-2-propyl- 1H-imidazole (5.52 g, 13.3 mmol) was dissolved in 50 mL of THF. The mixture was cooled at 0° C. under N2 and lithium diisopropylamide (7.3 mL of 2M in THF, 14.6 mmol) was added. After stirred at 0° C. for 15 minutes, a solution of o-phenoxybenzyl iodide (5.22 g, 16.8 mmol) in THF (15 mL) was added. The reaction mixture was warmed up to room temperature and stirred for 2 h. The mixture was partitioned between EtOAc and H2O. The two layers were separated. The aqueous layer was extracted with EtOAc. The combined organic solution was washed with brine, dried over MgSO4. It was concentrated and chromatographed on silica gel with 10-50% EtOAc/hexane to yield 2.35 g of the desired product. MS m/e 597.2, [M+H]+ ; IR (KBr): 1646 cm-1 for CO; 1H NMR (300 MHz, CDCl3): δ 0.95 (t, 3H, CH3), 1.22 (t, 3H, CH3), 1.65 (m, 2H, CH2), 2.57 (m, 2H, CH2), 2.82 (q, 2H, CH2), 2.98 (m, 2H, CH2), 3.10 (m, 2H, CH2) 5.42 (s, 2H, CH2Ar), 6.22 (t, 1H, ArH), 6.82 (d, 1H, ArH), 6.90 (d, 2H, ArH), 7.02 (m, 2H, ArH), 7.18 (d, 1H, ArH), 7.22 (m, 2H, ArH), 7.30 (m, 2H, ArH), 7.40 (d, 1H, ArH). ##STR66##

Workup

  1. temperatureThe reaction mixture was warmed up to room temperature
  2. stirringstirred for 2 h
  3. customThe mixture was partitioned between EtOAc and H2O
  4. customThe two layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washThe combined organic solution was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationIt was concentrated
  9. customchromatographed on silica gel with 10-50% EtOAc/hexane

Sources & evidence

ORD record
ord-e277f09057ca4995a2ec8e91e8b7953c
Source dataset
uspto-grants-1996_08
Patent number
US05545651

Reaction notes

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