4-Chlorobenzoyl chloride → methyl 9-(4-chlorobenzoyl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylate

HRID 527453Notes

Reaction equation

HRID 527453 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][CH:7]([C:15]([O:17][CH3:18])=[O:16])[CH2:6][C:5]2=1.CC([O-])(C)C.[Na+].[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1.[NH4+].[Cl-]>C1COCC1>[Cl:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:11]2[C:10]3[CH2:9][CH2:8][CH:7]([C:15]([O:17][CH3:18])=[O:16])[CH2:6][C:5]=3[C:4]3[C:12]2=[CH:13][CH:14]=[C:2]([F:1])[CH:3]=3)=[O:31])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 85014-Chlorobenzoyl chlorideHCID 25517Ammonium ChlorideHCID 23676156Sodium t-butoxideHCID 84612979methyl 6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylate

Product 1

HCID 89514784methyl 9-(4-chlorobenzoyl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylateYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled solution (ice bath, 0-5° C.) of methyl 6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylate (80 mg, 0.32 mmol) in THF (2.5 mL) was added tBuONa (2 M in THF, 194 μL, 0.39 mmol), and the mixture was stirred for 20 min at the low temperature. 4-Chlorobenzoyl chloride (67.9 mg, 0.39 mmol) was added and the reaction was aged overnight at room temperature. The reaction was poured into saturated aqueous NH4Cl (1 mL; provided in a 10 mL glass vial) and the organic compound extracted with ethyl acetate (3×3 mL), washed with brine and water, dried over Na2SO4 and concentrated in vacuo. The crude residue was subjected to flash chromatography (SiO2, ethyl acetate/hexane gradient) to afford the pure title compound as white crystalline solid in 14% yield (17 mg). C21H17ClFNO3, Mr=385.82; 1H NMR (400 MHz, DMSO-d6) d: 1.72-1.79 (m, 1H), 2.06-2.10 (m, 1H), 2.54-2.56 (m, 2H), 2.72-2.78 (m, 1H), 2.83-2.89 (m, 1H), 2.95 (dd, J=5.2/15.4 Hz, 1H), 3.65 (s, 3H), 6.99 (td, J=2.4/9.2 Hz, 1H), 7.23 (dd, J=4.6/9.0 Hz, 1H), 7.34 (dd, J=2.4/9.0 Hz, 1H), 7.62-7.69 (m, 4H); 19F NMR (282 MHz, DMSO-d6) d: −123.87 (q, 6′-F); LCMS (ESI) tR: 3.24 min (>99%, ELSD), m/z: 386.0 [M+1]+.

Workup

  1. waitthe reaction was aged overnight at room temperature

Sources & evidence

ORD record
ord-1c5de5fece1145dbbcc4718958e8698e
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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