Lithium Hexamethyldisilazide → HCID 71253372, compound

HRID 877472Notes

Reaction equation

HRID 877472 reaction equation
[Cl:1][C:2]1[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][C:8](=[O:26])[C:9]=1[N:10]2[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].[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[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([F:37])[C:8](=[O:26])[C:9]=1[N:10]2[S:16]([C:19]1[CH:20]=[CH:21][C:22]([CH3:23])=[CH:24][CH:25]=1)(=[O:18])=[O:17]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 15373214N-FluorobenzenesulfonamideHCID 67377761HCID 67377761, compound

Product 1

HCID 71253372HCID 71253372, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5,6-dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (300 mg, 0.7 mmol) in anhydrous THF (10 mL), cooled to −78° C., LiHMDS (1.47 mL, 1.4 mmol, 1M solution in THF) was added slowly. The reaction mixture was slowly warmed to 0° C. and stirred for an additional 30 min. while maintaining the temperature at 0° C. The reaction mixture was then cooled to −78° C. and N-fluoro benzene sulfonamide (0.22 g, 0.9 mmol), dissolved in THF (3 mL), was added dropwise. The reaction mixture was slowly warmed to 0° C. and stirred for 15 min during which time the reaction was complete. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×25 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant] to give the title compound (100 mg, 32%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.27 (d, J=9.5 Hz, 1H), 8.07 (d, J=8.5 Hz, 2H), 7.59 (d, J=9.5 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.30-5.13 (m, 1H), 3.71-3.66 (m, 1H), 3.35-3.28 (m, 1H), 2.58-2.55 (m, 1H), 2.43 (s, 3H), 2.40-2.38 (m, 1H)

Workup

  1. temperaturewhile maintaining the temperature at 0° C
  2. temperatureThe reaction mixture was then cooled to −78° C.
  3. additionwas added dropwise
  4. temperatureThe reaction mixture was slowly warmed to 0° C.
  5. stirringstirred for 15 min during which time the reaction
  6. customThe reaction was quenched with saturated NH4Cl
  7. extractionextracted with EtOAc (3×25 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude compound which
  11. customwas purified by column chromatography [EtOAc-hexane (1:9) as eluant]

Sources & evidence

ORD record
ord-1441267f926349f9a39a6cdf55e4acb0
Source dataset
uspto-grants-2015_03
Patent number
US08987319B2

Reaction notes

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