3-Fluorobenzyl chloride → 9-[(3-fluorophenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one

HRID 567266Notes

Reaction equation

HRID 567266 reaction equation
[C:1]([C:5]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:6]=1[C:7]1[C:8](=[O:18])[CH2:9][CH2:10][CH2:11][C:12]=1[NH:13]2)([O:3][CH3:4])=[O:2].[F:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23]Cl>CN(C=O)C.C(OCC)(=O)C>[F:19][C:20]1[CH:21]=[C:22]([CH2:23][N:13]2[C:12]3[CH2:11][CH2:10][CH2:9][C:8](=[O:18])[C:7]=3[C:6]3[C:14]2=[CH:15][CH:16]=[CH:17][C:5]=3[C:1]([O:3][CH3:4])=[O:2])[CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 2

HCID 99743-Fluorobenzyl chlorideHCID 11368514methyl 4-oxo-2,3,4,9-tetrahydro-1H-carbazole-5-carboxylate

Product 1

HCID 227386219-[(3-fluorophenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-oneYield 37.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

40% Methanolic Triton B (2.06 mL, 4.53 mM) was slowly added dropwise to a solution of 5-carbomethoxy-1,2-dihydro-9H-carbazol-4(3H)-one (930.0 mg, 3.82 mM) in 5 mL of DMF at 0° C. After 5 minutes, 3-fluorobenzyl chloride (664.0 mg, 4.59 mM) was added and the resultant mixture stirred at 0° C. for 3 h, then at room temperature for 20 hours. The mixture was diluted with ethyl acetate, washed three times with 1 N HCl, three times with H2O, once with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient methylene chloride/ethyl acetate) to afford 502.3 mg (37%) of the 9-[(3-fluorophenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one as a yellow foam. 1H NMR (CDCl3) δ 7.4-7.2 (m, 4H), 6.9 (m, 1H), 6.7 (m, 2H), 5.35 (s, 2H), 4.05 (s, 3H), 2.9 (t, 2H, J=6 Hz), 2.65 (t, 2H, J=6 Hz), and 2.3 (m, 2H). IR (CHCl3, cm−1) 3050, 2950, 1725, 1654, 1464, 1451, 1440, 1288 and 1119. MS (ES) m/e 350, 352.

Workup

  1. waitat room temperature for 20 hours
  2. washwashed three times with 1 N HCl, three times with H2O
  3. dry with materialonce with saturated brine, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (elution with gradient methylene chloride/ethyl acetate)

Sources & evidence

ORD record
ord-d518258b857c442b97b3e920744ed577
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

Loading…