Ethyl 4-iodobenzoate → Ethyl 4-[4,4-dimethylthiochroman-6-yl-ethynyl]benzoate

HRID 1193617Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1193617
[CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[CH:13])[CH:10]=2)[S:5][CH2:4][CH2:3]1.C([Li])CCC.I[C:21]1[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=1>O1CCCC1.CCCCCC.[Cl-].[Cl-].[Zn+2]>[CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[C:13][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH:10]=2)[S:5][CH2:4][CH2:3]1

Komponenten

7

Edukt 3

HCID 142891Ethyl 4-iodobenzoateHCID 109325396-Ethynyl-4,4-dimethylthiochromanHCID 178418339Butyllithium

Produkt 1

HCID 9884783Ethyl 4-[4,4-dimethylthiochroman-6-yl-ethynyl]benzoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 8028TetrahydrofuranLösungsmittel4×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Reaction vessels used in this procedure were flame dried under vacuum and all operations carried out in an oxygen-free, argon or nitrogen atmosphere. To a solution of 533.9 mg (2.6389 mmol) of 4,4-dimethyl-6-ethynylthiochroman (from Example 4) in 4 ml of dry tetrahydrofuran at 0° C. was added dropwise 1.7 ml of 1.6M (2.72 mmol) n-butyl lithium in hexane. This was stirred at 0° C. for 10 minutes and at room temperature for 15 minutes, cooled again to 0° C. and then treated with a solution of 410 mg (3.005 mmol) of fused ZnCl2 in 4 ml dry tetrahydrofuran using a double ended needle. Thereafter, the solution was stirred at 0° C. for 45 minutes, then at room temperature for 20 minutes. A solution of 724.4 mg (2.6243 mmol) of ethyl 4-iodobenzoate (from Example 5) in 4 ml dry tetrahydrofuran was transferred by double ended needle into a suspension of 520 mg (0.45 mmol) of tetrakistriphenylphosphine palladium in 5 ml dry tetrahydrofuran and stirred at room temperature for 20 minutes, then treated by double ended needle with the solution of the alkynyl zinc chloride prepared above. This mixture was stirred at room temperature for 18 hours, then quenched with ice and 30 ml 3N hydrogen chloride. Product was recovered by extraction with 3×75 ml ether. Ether fractions were combined and washed successively with saturated NaHCO3 and saturated NaCl solutions and dried (MgSO4). Solvent was removed in vacuo and the residue purified by flash chromatography (silica; 5% ethyl acetate in hexane) followed by HPLC (Whatman Partisil M-9 10/50; 4% ethyl acetate in hexane) to give the title compound as a colorless oil. PMR (CDCl3) :δ 1.36 (6H), 1.42 (3H, t, J~7 Hz), 1.93-1.99 (2H, m), 3.03-3.08 (2H, m), 4.40 (2H, q, J~7 Hz), 7.09 (1H, d, J~8.4 Hz), 7.22 (1H, dd, J~8.4 Hz, 2.1 Hz), 7.56 (1H, d, J~2.11 Hz), 7.59 (2H, d, J~7.8 Hz), 8.04 (2H, d, J~7.8 Hz).

Aufarbeitung

  1. customReaction vessels
  2. temperaturewere flame
  3. customdried under vacuum
  4. temperaturecooled again to 0° C.
  5. stirringThereafter, the solution was stirred at 0° C. for 45 minutes
  6. waitat room temperature for 20 minutes
  7. stirringstirred at room temperature for 20 minutes
  8. customprepared above
  9. stirringThis mixture was stirred at room temperature for 18 hours
  10. customquenched with ice and 30 ml 3N hydrogen chloride
  11. customProduct was recovered by extraction with 3×75 ml ether
  12. washwashed successively with saturated NaHCO3 and saturated NaCl solutions
  13. dry with materialdried (MgSO4)
  14. customSolvent was removed in vacuo
  15. customthe residue purified by flash chromatography (silica; 5% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-f94108d4922341e0ba621942785e5230
Quelldatensatz
uspto-grants-1989_03
Patentnummer
US04810804

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