Tetrahydrofuran → (4-Hydroxy-tetrahydro-pyran-4-yl)-(6-trifluoromethyl-pyridin-3-yl)-acetonitrile

HRID 512172

反応式

HRID 512172 の反応式
[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.C1COCC1.[O:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[OH:25][C:22]1([CH:9]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:12])([F:1])[F:13])=[CH:4][CH:5]=2)[C:10]#[N:11])[CH2:23][CH2:24][O:19][CH2:20][CH2:21]1

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 508511273-Pyridineacetonitrile, 6-(trifluoromethyl)-

生成物 1

HCID 86716199(4-Hydroxy-tetrahydro-pyran-4-yl)-(6-trifluoromethyl-pyridin-3-yl)-acetonitrile収率 47.1%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-78 °C

実験手順

2-(6-(Trifluoromethyl)pyridin-3-yl)acetonitrile (260 mg, 1.4 mmol) was dissolved in THF (3 mL, 30 mmol) under Ar and cooled at −78° C. A solution of 0.6 Ni sodium bis(trimethylsilyl)amide in toluene (3.49 mL) was added dropwise. After stirring at −78° C. for 4 hours the reaction was allowed to reach −50° C. for 30 minutes. Then tetrahydro-4H-pyran-4-one (0.189 mL, 2.10 mmol) was added dropwise at −60° C. and the reaction was kept at this temperature for 45 minutes. To the reaction was added sat. aq. NH4Cl (10 mL) and it was extracted AcOEt (3×20 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography to yield 2-(4-Hydroxytetrahydro-2H-pyran-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrile (189 mg, 0.660 mmol, 47%).

後処理

  1. waitto reach −50° C. for 30 minutes
  2. waitthe reaction was kept at this temperature for 45 minutes
  3. extractionwas extracted AcOEt (3×20 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography

出典と根拠

ORDレコード
ord-e6b004e343b74bc09a6468ec2756c898
出典データセット
uspto-grants-2015_08
特許番号
US09102591B2

関連ノート

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