Potassium Hydroxide → HCID 9838040, compound

HRID 397313Notes

Reaction equation

HRID 397313 reaction equation
COC(=O)[NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH3:13])=[CH:7][C:6]=1[C:14]#[C:15][CH2:16][CH2:17][CH2:18]Cl.C(OC1C=CC2[N:29]3CC[CH2:35][C:28]3=[CH:27]C=2C=1)C.[OH-].[K+]>C(#N)C.[Pd](Cl)Cl>[CH2:12]([O:11][C:8]1[CH:9]=[CH:10][C:5]2[N:4]3[CH2:18][CH2:17][CH2:16][C:15]3=[C:14]([CH2:27][C@@H:28]([NH2:29])[CH3:35])[C:6]=2[CH:7]=1)[CH3:13]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 86586308HCID 86586308, compound

Product 1

HCID 9838040HCID 9838040, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Iodoethane (15.8 mL, 220.64 mmol) and potassium carbonate (28.4 g, 220.05 mmol) were added to [2-(5-Chloro-pent-1-ynyl)-4-hydroxy-phenyl]-carbamic acid methyl ester (39 g, 145.68 mmol) in N,N-dimethylformamide (300 mL). The mixture was stirred 3 h at room temperature. The mixture was poured into 1M pH7 phosphate buffer and the organic phase extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and evaporated to dryness. The oily residue was purified by column chromatography on silica gel (6:1 to 5:1 hexane/ethyl acetate eluant) to afford the product as an oil (29 g, 67% over two steps) which solidified upon standing in the refrigerator. m.p. 55-56° C. 6-Ethoxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]indene [2-(5-Chloro-pent-1-ynyl)-4-ethoxy-phenyl]-carbamic acid methyl ester (28.5 g, 96.36 mmol) was dissolved in acetonitrile (600 mL). Palladium (II) chloride (0.9 g, 5.08 mmol) was added and the mixture was heated 2 h at 70° C. The dark mixture was cooled to room temperature and filtered through a small pad of celite, while washing the pad with acetonitrile. The solvent was evaporated to dryness and the brown residue (30 g) taken up in tert-butanol (600 mL). Powdered potassium hydroxide (22 g, 392.09 mmol) was added and the mixture stirred 40 min in an oil-bath at 105° C. The mixture was cooled, poured onto ice and extracted twice with ethyl acetate. The combined organic phases were washed with water, brine, dried over sodium sulfate and evaporated. The brown residue was purified by column chromatography on silica gel (5:1 hexane/ethyl acetate) to afford the product as an off-white solid (13.4 g, 69%). m.p.101-102° C.

Workup

  1. temperatureThe dark mixture was cooled to room temperature
  2. filtrationfiltered through a small pad of celite
  3. washwhile washing the pad with acetonitrile
  4. customThe solvent was evaporated to dryness
  5. temperatureThe mixture was cooled
  6. additionpoured onto ice
  7. extractionextracted twice with ethyl acetate
  8. washThe combined organic phases were washed with water, brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customThe brown residue was purified by column chromatography on silica gel (5:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-edc97d8960a5469ca5a87ba455e8ef8d
Source dataset
uspto-grants-2003_08
Patent number
US06610685B2

Reaction notes

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