Chlorotrimethylsilane → 7-Fluoro-5-methyl-10-(trimethylsilyl)-5,10-dihydroindeno[1,2-b]indole

HRID 2369226Notes

Reaction equation

HRID 2369226 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:18][C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:7]=3[N:8]([CH3:11])[C:9]=2[CH:10]=1.[Li]CCCC.[CH3:24][Si:25](Cl)([CH3:27])[CH3:26]>CCOCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH:18]([Si:25]([CH3:27])([CH3:26])[CH3:24])[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:7]=3[N:8]([CH3:11])[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 58403402HCID 58403402, compoundHCID 178418339Butyllithium

Product 1

HCID 584033927-Fluoro-5-methyl-10-(trimethylsilyl)-5,10-dihydroindeno[1,2-b]indoleYield 2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
25 °C

Procedure

Compound 31b (as a 2:1.1 mixture of regioisomers, 1.61 g, 6.79 mmol) was dissolved in anhydrous ether (46 mL) and the reaction mixture was immersed in a 25° C. water bath. n-BuLi (1.5M in hexanes, 5.25 mL, 7.87 mmol) was added dropwise via syringe pump over one hour. Following addition of base, the reaction mixture was stirred for one hour at 25° C. and then cooled to −78° C. TMSCl (1.81 mL, 14.25 mmol) was added rapidly via syringe and the resulting mixture was immediately warmed to 25° C. for 1.5 hours. The reaction mixture was diluted with 20 mL ether, filtered, and concentrated in vacuo to yield a dark green solid which was subsequently purified by multiple rounds of flash column chromatography (15:1 hexanes-ethyl acetate; 20:1 hexanes-ethyl acetate) to give the desired regioisomer in pure form and 2% yield. This low yield is a result of the similar polarities of regioisomers, which render separation a challenge. Spectral data are reported for the mixture that remained following purification of a small percentage of the desired regioisomer. As a result, product ratios do not represent those of the original product mixture. 1H NMR (600 MHz, CDCl3): δ 7.74 (d, 1H, J=7.8 Hz), 7.71 (d, 0.5H, J=7.2 Hz), 7.51-7.55 (m, 2.5H), 7.31-7.34 (m, 1.5H), 7.21-7.24 (td, 1H, J=7.2, 1.2 Hz), 7.18-7.21 (td, 0.5H, J=7.2, 1.2 Hz), 7.17 (d, 1H, J=7.8 Hz), 7.12-7.14 (m, 1H), 7.05-7.07 (dd, 0.5H, J=9.9, 2.4 Hz), 6.87-6.91 (m, 0.5H), 6.80-6.83 (ddd, 1H, J=10.2, 8.4, 1.2 Hz), 4.10 (s, 3H), 4.05 (s, 1.5H), 3.93 (s, 1H), 3.75 (s, 0.5H), −0.04 (s, 4.5H), −0.98 (d, 9H, J=0.6 Hz); 13C NMR (150 MHz, CDCl3): δ 159.3 (d, J=237.0 Hz), 156.0 (d, J=246 Hz), 150.4, 149.6, 144.3 (d, J=10.5 Hz), 143.6 (d, J=3.0 Hz), 143.0, 142.0 (d, J=12.0 Hz), 133.4, 132.7, 125.1, 124.9, 124.6, 124.6, 123.8, 123.52, 123.1, 121.3 (d, J=9.0 Hz), 120.6 (d, J=10.5 Hz), 120.3 (d, J=21.0 Hz), 117.6, 117.3, 113.0 (d, J=21.0 Hz), 107.4 (d, J=24.0 Hz), 105.6, 105.5, 104.4 (d, J=19.5 Hz), 96.2 (d, J=27.0 Hz), 37.3, 36.8, 31.5, 31.3, −2.42, −2.52 (d, J=3.0 Hz); 19F NMR (CD3CD, 376 MHz): δ −117.1 (d, J=6.8 Hz), −120.5-−120.1 (td, J=9.4, 3.8 Hz) FTIR: cm−1 3057, 2953, 1621, 1572, 1436, 1360, 1248, 1048, 839, 756, 727.

Workup

  1. customwas immersed in a 25° C.
  2. additionaddition of base
  3. temperaturecooled to −78° C
  4. temperaturethe resulting mixture was immediately warmed to 25° C. for 1.5 hours
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield a dark green solid which
  8. customwas subsequently purified by multiple rounds of flash column chromatography (15:1 hexanes-ethyl acetate; 20:1 hexanes-ethyl acetate)
  9. customto give the desired regioisomer in pure form and 2% yield
  10. customThis low yield
  11. customa result of the similar polarities of regioisomers, which
  12. customseparation a challenge
  13. custompurification of a small percentage of the desired regioisomer

Sources & evidence

ORD record
ord-d141bf07308d478da62ac5dd2c7c0968
Source dataset
uspto-grants-2014_04
Patent number
US08703936B2

Reaction notes

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