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

HRID 248185

반응식

HRID 248185 반응식
[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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 12679Hexamethylphosphoramide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c17b06858bce4869b87078601f16008e
출처 데이터셋
uspto-grants-1993_05
특허 번호
US05208344

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