Acetone → 4-(1-Hydroxy-1-methyl-ethyl)-3-methyl-benzoic acid

HRID 1478454

Reaktionsgleichung

Reaktionsgleichung von HRID 1478454
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].C([Li])CCC.[CH3:17][C:18]([CH3:20])=[O:19].Cl>O1CCCC1.[OH-].[Na+]>[OH:19][C:18]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11])([CH3:20])[CH3:17]

Komponenten

7

Edukt 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 821314-Bromo-3-methylbenzoic acidHCID 178418339Butyllithium

Produkt 1

HCID 681532454-(1-Hydroxy-1-methyl-ethyl)-3-methyl-benzoic acidAusbeute 42,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

4-Bromo-3-methyl-benzoic acid (3.96 g, 18.4 mmol) was dissolved in tetrahydrofuran (100 mL) and the solution was cooled to −78° C. n-Butyllithium in hexanes (16.2 mL of 2.5 M, 41 mmol) was added dropwise over 20 minutes. The reaction mixture was allowed to stir for 30 minutes at −78° C. and then acetone (1.35 mL, 18.4 mmol) was added in a drop-wise manner. The reaction mixture was allowed to stir for 30 minutes at −78° C., and then it was allowed to warm to room temperature. The reaction mixture was then diluted with 100 mL of 1M aqueous sodium hydroxide. The organic layer was discarded and then the aqueous layer was made acidic with 4M aqueous hydrochloric acid. The aqueous layer was then extracted 3 times with ethyl acetate. The combined extracts were dried over sodium sulfate and then evaporated to dryness. The crude material was further purified on silica gel utilizing a gradient of 0-10% methanol in dichloromethane to give 4-(1-hydroxy-1-methyl-ethyl)-3-methyl-benzoic acid (1.51 g, 42%). 1H NMR (400 MHz, DMSO) δ 12.74 (s, 1H), 7.68 (dd, J=3.9, 2.5 Hz, 2H), 7.55 (d, J=8.7 Hz, 1H), 5.06 (s, 1H), 2.56 (s, 3H), 1.51 (s, 6H).

Aufarbeitung

  1. additionwas added dropwise over 20 minutes
  2. stirringto stir for 30 minutes at −78° C.
  3. temperatureto warm to room temperature
  4. extractionThe aqueous layer was then extracted 3 times with ethyl acetate
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude material was further purified on silica gel utilizing a gradient of 0-10% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-c5adf216169d43a4988c0ef2f93064ec
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403839B2

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