Acetic Acid → alpha,alpha-Dimethyl-6-methoxy-2-naphthaleneacetic acid methyl ester

HRID 1655558

Reaktionsgleichung

Reaktionsgleichung von HRID 1655558
[CH3:1][O:2][C:3](=[O:18])[CH:4]([CH3:17])[C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=2)[CH:6]=1.[CH:19]([N-]C(C)C)(C)C.[Li+].C1CCCCC1.CI.C(O)(=O)C>O1CCCC1>[CH3:1][O:2][C:3](=[O:18])[C:4]([CH3:19])([CH3:17])[C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH3:16])[CH:11]=2)[CH:6]=1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 6328Methyl iodideHCID 8078CyclohexaneHCID 529084(RS)-Naproxen methyl esterHCID 2724682Lithium diisopropylamide

Produkt 1

HCID 15030202alpha,alpha-Dimethyl-6-methoxy-2-naphthaleneacetic acid methyl esterAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (α-methyl-6-methoxy-2-naphthaleneacetic acid methyl ester (12.2 g, 50 mmol) in tetrahydrofuran (100 ml) at -70° C. is added a solution of lithium diisopropylamide in cyclohexane (50 ml, 1.5 equiv). After 20 minutes, methyl iodide (4.0 ml, 1.3 equiv) is added followed by hexamethylphosphoraniide (20 ml). After allowing the reaction mixture to warm to room temperature and stir 16 hours, the reaction is quenched by addition of acetic acid (4.3 ml, 75 mmol). The solvent is then removed and the residue is partitioned between ethyl acetate and water. The organic layer is washed with water 3 times and finally with brine. After drying over magnesium sulfate, the organic extract is evaporated to afford a crude solid. Recrystallization of this solid from hexane affords 8.56 g (66%) of α,α-dimethyl-6-methoxy-2-naphthaleneacetic acid methyl ester as white crystals, m.p. 97°-98° C. A solution of this ester (7.4 g, 28.6 mmol) in 48% HBr (50 ml) and acetic acid (50 ml) is refluxed for 3 hours. After the reaction mixture is cooled to room temperature, 0.8 L of water is added and the reaction mixture is extracted with ethyl acetate 5 times. The combined organic extract is washed sequentially with saturated sodium bicarbonate solution and water. After drying over magnesium sulfate, the organic extract is evaporated to afford 6.1 g (93%) of α,α-dimethyl-6-hydroxy-2-naphthaleneacetic acid as white crystals, m.p. 208°-210° C. The title compound is prepared according to the method of Example 7 using α,α-dimethyl-6-hydroxy-2-naphthaleneacetic acid. A white solid is obtained having a melting point of 207°-209° C.

Aufarbeitung

  1. customThe solvent is then removed
  2. customthe residue is partitioned between ethyl acetate and water
  3. washThe organic layer is washed with water 3 times and finally with brine
  4. dry with materialAfter drying over magnesium sulfate
  5. extractionthe organic extract
  6. customis evaporated
  7. customto afford a crude solid
  8. customRecrystallization of this solid from hexane

Quellen und Nachweise

ORD-Eintrag
ord-0ae13aa46a2b4de08bbd10153185de52
Quelldatensatz
uspto-grants-1993_10
Patentnummer
US05250693

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