Hydrochloric Acid → 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

HRID 61852Notes

Reaction equation

HRID 61852 reaction equation
Br[C:2]1[C:3]([C:31]#[N:32])=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[C:11]([CH3:16])([CH3:15])[C:10]3[CH:17]=[C:18]([O:21][CH2:22][C@H:23]4[CH2:27][O:26][C:25]([CH3:29])([CH3:28])[O:24]4)[CH:19]=[CH:20][C:9]=3[C:8](=[O:30])[C:7]2=1.[Cl-].[Li+].[CH3:35][Sn](C)(C)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Cl>CN(C=O)C>[CH3:29][C:25]1([CH3:28])[O:24][C@@H:23]([CH2:22][O:21][C:18]2[CH:19]=[CH:20][C:9]3[C:8](=[O:30])[C:7]4[C:6]5[C:14](=[C:2]([CH3:35])[C:3]([C:31]#[N:32])=[CH:4][CH:5]=5)[NH:13][C:12]=4[C:11]([CH3:16])([CH3:15])[C:10]=3[CH:17]=2)[CH2:27][O:26]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11661TetramethyltinHCID 75806TricyclohexylphosphineHCID 433294Lithium ChlorideHCID 668348924-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Product 1

HCID 668348858-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 μmol) and lithium chloride (7.70 mg, 181.7 μmol) were dissolved in DMF (1.00 mL), added with tetramethyl tin (12.5 μL, 90.84 μmol), tetrakistriphenylphosphine palladium (3.50 mg, 6.056 μmol) and tricyclohexylphosphine (toluene solution, 20 wt %, 17.0 mg, 3.028 μmol), and the mixture was stirred at 100° C. for 24 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile as a crude product (20.9 mg, 80%).

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with water, saturated aqueous solution of sodium bicarbonate and saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe residues obtained
  6. concentrationafter concentration under reduced pressure
  7. customwere purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d0903f5640e849a898af16fc3822cc07
Source dataset
uspto-grants-2016_09
Patent number
US09440922B2

Reaction notes

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