Formic Acid → HCID 66835640, Verbindung

HRID 40446Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 40446
I[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.[O:10]([CH2:20][CH2:21][CH:22]1[CH2:27][CH:26]2[CH2:28][CH:23]1[CH:24]=[CH:25]2)[CH2:11][CH2:12][CH:13]1[CH2:18][CH:17]2[CH2:19][CH:14]1[CH:15]=[CH:16]2.C(N([CH2:34][CH3:35])CC)C.[CH:36]([OH:38])=O>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:10]([CH2:20][CH2:21][CH:22]1[CH2:27][CH:26]2[CH2:28][CH:23]1[CH2:24][CH:25]2[C:2]1[CH:3]=[CH:4][C:36]([OH:38])=[C:34]([CH3:35])[CH:7]=1)[CH2:11][CH2:12][CH:13]1[CH2:18][CH:17]2[CH2:19][CH:14]1[CH2:15][CH:16]2[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1

Komponenten

7

Edukt 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 1437134-Iodo-2-methylphenolHCID 67607440HCID 67607440, Verbindung

Produkt 1

HCID 66835640HCID 66835640, VerbindungAusbeute 128,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

An appropriately sized and equipped reaction vessel was charged with 4-iodo-2-methylphenol (75.7 g, 323 mmol) in 380 mL DMF. To that was added Pd(PPh3)4 (3.56 g, 3.08 mmol) at room temperature giving a light yellow solution. Then, 5,5′-(oxybis(ethane-2,1-diyl))bis(bicyclo[2.2.1]hept-2-ene) (39.8 g, 154 mmol), 100 ml dimethylformamide (DMF), and triethylamine (65 mL, 462 mmol) were added and the mixture stirred as formic acid (17.7 g, 14.5 mL 385 mmol) was added drop wise within 5 minutes. The reaction temperature rose from 20° C. to 25° C. after which external heating was applied. At 70° C., an exothermic reaction began and the temperature quickly climbed to 82° C. within 10 minutes accompanied by color changes from light yellow to orange to black. The reaction was monitored by GC and after stirring at 75° C. for 96 h an aliquot GC indicated the reaction was complete. The reaction mixture was allowed to cool to room temperature and was poured into 2000 mL distilled water. The aqueous mixture was extracted with (3×1500 mL) MTBE, the extracts were filtered through a Celite® filtering aid pad to remove palladium particles and then washed with (2×1 L) water, (2×1 L) brine and (2×1 L) 5% aqueous LiCl to remove residual DMF. The resulting MTBE solution was dried over sodium sulfate, filtered, and the solvent rotary evaporated to give 94 g of a brown liquid. The 94 g of crude PP475 was adsorbed onto 120 g silica and chromatographed over an additional 1 kg of silica eluting with heptane-EtOAc mixtures. The concentrated purified fractions yielded 43 g (59% yield) of PP475 as a clear viscous oil with >98.0% purity by NMR. NMR and MS were consistent with the desired structure.

Aufarbeitung

  1. customequipped
  2. customreaction vessel
  3. customgiving a light yellow solution
  4. additionwas added drop wise within 5 minutes
  5. customrose from 20° C. to 25° C.
  6. temperatureexternal heating
  7. customAt 70° C., an exothermic reaction
  8. temperatureto cool to room temperature
  9. additionwas poured into 2000 mL
  10. distillationdistilled water
  11. extractionThe aqueous mixture was extracted with (3×1500 mL) MTBE
  12. filtrationthe extracts were filtered through a Celite®
  13. filtrationfiltering aid pad
  14. customto remove palladium particles
  15. washwashed with (2×1 L) water, (2×1 L) brine and (2×1 L) 5% aqueous LiCl
  16. customto remove residual DMF
  17. dry with materialThe resulting MTBE solution was dried over sodium sulfate
  18. filtrationfiltered
  19. customthe solvent rotary evaporated

Quellen und Nachweise

ORD-Eintrag
ord-be2f4adf668645ae8bbb2b9b9271101e
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530133B2

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