Tetrahydrofuran → 3-(4'-Ethoxy-2,2',3,3'-tetrafluorobiphenyl-4-yl)-6-(4-propylcyclohexyl)tetrahydropyran-2-one

HRID 1941724ノート

反応式

HRID 1941724 の反応式
C1COCC1.[CH2:6]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([OH:24])=[O:23])=[C:17]([F:25])[C:16]=2[F:26])=[C:11]([F:27])[C:10]=1[F:28])[CH3:7].C([Li])CCC.[CH2:34]([C@H:37]1[CH2:42][CH2:41][C@H:40]([CH:43]2[CH2:46][CH2:45]O2)[CH2:39][CH2:38]1)[CH2:35][CH3:36]>C(O)=O>[CH2:6]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:36][CH2:35][CH:34]([CH:37]4[CH2:38][CH2:39][CH:40]([CH2:43][CH2:46][CH3:45])[CH2:41][CH2:42]4)[O:23][C:22]3=[O:24])=[C:17]([F:25])[C:16]=2[F:26])=[C:11]([F:27])[C:10]=1[F:28])[CH3:7]

参加物

6

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 679923862-(4'-Ethoxy-2,2',3,3'-tetrafluorobiphenyl-4-yl)acetic acidHCID 178418339ButyllithiumHCID 178447926HCID 178447926、化合物

生成物 1

HCID 585356163-(4'-Ethoxy-2,2',3,3'-tetrafluorobiphenyl-4-yl)-6-(4-propylcyclohexyl)tetrahydropyran-2-one収率 87%

試薬・触媒・溶媒 1

HCID 284Formic Acid溶媒

反応条件

温度
-5 °C

実験手順

THF (50 ml) was added to 2-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)acetic acid (10) (2.0 g) prepared in the eighth step. The solution was cooled to −5° C., and n-butyllithium (1.59 M in n-hexane; 7.66 ml) was added dropwise. After the addition had been completed, the reaction mixture was returned to room temperature, and the stirring was continued for 30 minutes. The solution was then cooled to −65° C., and 2-(trans-4-propyl-cyclohexyl)-oxetane (5) (1.0 g) in a THF (5 ml) solution and a boron trifluoride-diethyl ether complex (0.86 g) were added dropwise. After the addition had been completed, the reaction mixture was returned to room temperature, and a 10% aqueous solution of formic acid (100 ml) was added to give two layers. The water layer was extracted with toluene (20 ml) three times and the combined organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (silica gel: 200 g, eluent: heptane/ethyl acetate=90/10 by volume) to give 3-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)-6-(4-propylcyclohexyl)tetrahydropyran-2-one (11) (2.35 g) in 86.1% yield.

後処理

  1. customprepared in the eighth step
  2. additionAfter the addition
  3. customwas returned to room temperature
  4. temperatureThe solution was then cooled to −65° C.
  5. additionAfter the addition
  6. customwas returned to room temperature
  7. customto give two layers
  8. extractionThe water layer was extracted with toluene (20 ml) three times
  9. washthe combined organic layer was washed with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationThe solvent was distilled off under reduced pressure
  12. customThe residue was purified by silica gel chromatography (silica gel: 200 g, eluent: heptane/ethyl acetate=90/10 by volume)

出典と根拠

ORDレコード
ord-d3d8b68963394fd8b466d1ea3f3d8c8f
出典データセット
uspto-grants-2013_03
特許番号
US08389073B2

反応ノート

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