Lithium Hexamethyldisilazide → HCID 67377721, compound

HRID 877466Notes

Reaction equation

HRID 877466 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[Cl:15])[N:11]([S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17])[C:10]1[C:9](=[O:26])[CH2:8][CH2:7][CH2:6][C:5]2=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:37]NS(C1C=CC=CC=1)(=O)=O>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[Cl:15])[N:11]([S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17])[C:10]1[C:9](=[O:26])[CH:8]([F:37])[CH2:7][CH2:6][C:5]2=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 15373214N-FluorobenzenesulfonamideHCID 67362572HCID 67362572, compound2×

Product 1

HCID 67377721HCID 67377721, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

6,7-Dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (intermediate 1c) (420 mg, 1.02 mmol) dissolved in anhydrous THF (10 mL) and cooled to −78° C. was mixed with LiHMDS (1.13 mL, 1.1 mmol, 1M solution in THF). The reaction mixture was slowly warmed to 0° C., stirred for an additional 30 min. at 0° C., then cooled to −78° C. and N-fluoro benzene sulfonamide (0.31 g, 1.3 mmol) was added. The resulting mixture was slowly warmed to room temperature and stirred for 15 min., quenched with saturated NH4Cl and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, the solvent was removed under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (7:93) as eluant] to obtain the title compound (160 mg, 37%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.53 (s, 1H), 8.082 (d, J=8.0 Hz, 2H), 7.69 (s, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.26-5.13 (m, 1H), 3.14-3.11 (m, 1H), 3.01-2.95 (m, 1H), 2.62-2.55 (m, 1H), 2.42 (s, 3H), 2.38-2.41 (m, 1H).

Workup

  1. temperatureThe reaction mixture was slowly warmed to 0° C.
  2. temperaturecooled to −78° C.
  3. temperatureThe resulting mixture was slowly warmed to room temperature
  4. stirringstirred for 15 min.
  5. customquenched with saturated NH4Cl
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. customthe solvent was removed under reduced pressure
  9. customto give the crude compound which
  10. customwas purified by column chromatography [EtOAc-hexane (7:93) as eluant]

Sources & evidence

ORD record
ord-6d6943c72a7741bbbd111baaa97845eb
Source dataset
uspto-grants-2015_03
Patent number
US08987319B2

Reaction notes

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