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

HRID 248185

反応式

HRID 248185 の反応式
[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.CN(C)P(N(C)C)(N(C)C)=O>[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

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 12679Hexamethylphosphoramide溶媒

実験手順

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 min, methyl iodide (4.0 ml, 1.3 equiv) is added followed by hexamethylphosphoramide (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.

後処理

  1. customat -70 °
  2. customThe solvent is then removed
  3. customthe residue is partitioned between ethyl acetate and water
  4. washThe organic layer is washed with water 3 times and finally with brine
  5. dry with materialAfter drying over magnesium sulfate
  6. extractionthe organic extract
  7. customis evaporated
  8. customto afford a crude solid
  9. customRecrystallization of this solid from hexane

出典と根拠

ORDレコード
ord-c17b06858bce4869b87078601f16008e
出典データセット
uspto-grants-1993_05
特許番号
US05208344

関連ノート

読み込み中…