Ammonium Chloride → 5-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]-2-trimethylsilanylethynyltetrahydropyran-2-ol

HRID 605455ノート

反応式

HRID 605455 の反応式
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].C([Li])CCC.[CH2:12]([O:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][CH:24]([CH:27]3[CH2:32][O:31][C:30](=[O:33])[CH2:29][CH2:28]3)[CH2:23][CH2:22]2)=[C:17]([F:36])[C:16]=1[F:37])[CH3:13].[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH2:12]([O:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][CH:24]([CH:27]3[CH2:32][O:31][C:30]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])([OH:33])[CH2:29][CH2:28]3)[CH2:23][CH2:22]2)=[C:17]([F:36])[C:16]=1[F:37])[CH3:13]

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 66111TrimethylsilylacetyleneHCID 668767205-[4-(4-Ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-oneHCID 178418339Butyllithium

生成物 1

HCID 668769855-[4-(4-Ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]-2-trimethylsilanylethynyltetrahydropyran-2-ol収率 92.6%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

実験手順

2.55 g of trimethylsilylacetylene was dissolved in 20 mL THF, and then 15.7 mL of a 1.66 M hexane solution of n-butyllithium was added dropwise thereto at −70° C., followed by stirring at that temperature for 1 hour. To the resulting solution, a solution containing 9.12 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one obtained in the twelfth step of Example 1 dissolved in 30 mL of THF was added dropwise at −70° C., followed by stirring at that temperature for 1 hour, and then the temperature of the solution was gradually increased to room temperature. The reaction product was poured into 50 mL of a saturated ammonium chloride aqueous solution, and the mixture was extracted with diethyl ether. The organic layer was washed with water and concentrated under reduced pressure. The resulting brown residue was purified by silica gel column chromatography to provide 10.7 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]-2-trimethylsilanylethynyltetrahydropyran-2-ol as a brown solid.

後処理

  1. customat −70° C.
  2. customobtained in the twelfth step of Example 1
  3. additionwas added dropwise at −70° C.
  4. stirringby stirring at that temperature for 1 hour
  5. extractionthe mixture was extracted with diethyl ether
  6. washThe organic layer was washed with water
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting brown residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-1efc1bba8bdc4dba93b79a9cbb07095c
出典データセット
uspto-grants-2011_03
特許番号
US07914862B2

反応ノート

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