Triphenylphosphine → 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

HRID 61828

Reaction equation

HRID 61828 reaction equation
[Cl:1][C:2]1[C:14]([F:15])=[C:13]2[C:5]([C:6]3[C:7](=[O:23])[C:8]4[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:9]=4[C:10]([CH3:17])([CH3:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[CH3:24][C:25]1([CH3:32])[O:29][C@@H:28]([CH2:30]O)[CH2:27][O:26]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OCC)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:14]([F:15])=[C:13]2[C:5]([C:6]3[C:7](=[O:23])[C:8]4[CH:21]=[CH:20][C:19]([O:22][CH2:30][C@H:28]5[CH2:27][O:26][C:25]([CH3:32])([CH3:24])[O:29]5)=[CH:18][C:9]=4[C:10]([CH3:17])([CH3:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 736057(+)-SolketalHCID 668346463-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

Product 1

HCID 668344233-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

3-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-3, 20.0 mg, 0.061 mmol) was dissolved in THF (0.25 mL), added with ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (9.8 μL, 0.079 mmol), triphenylphosphine (20.7 mg, 0.079 mmol) and diethyl azodicarboxylic acid (35.9 μl, 0.079 mmol), and then stirred at 40° C. for 5 hr. The reaction solution was concentrated under reduced pressure, and the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the intermediate, 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one. This compound was dissolved in THF (0.10 mL) and MeOH (0.08 ml), added with sulfuric acid (0.5 M, 0.045 ml), and then stirred at 60° C. for 1 hr. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The yellow solid obtained after concentration under reduced pressure was washed with methylene chloride/hexane solvent and filtered to obtain the title compound (4.3 mg, 18%).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. customthe resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2967183ca22b41af8009032890679a04
Source dataset
uspto-grants-2016_09
Patent number
US09440922B2

Linked notes

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