Benzyl Alcohol → 2-(Benzyloxy)-4-bromo-6-fluorobenzonitrile

HRID 2367541ノート

反応式

HRID 2367541 の反応式
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:11][C:12]1[CH:19]=[C:18](F)[C:15]([C:16]#[N:17])=[C:14]([F:21])[CH:13]=1.O>C1COCC1>[Br:11][C:12]1[CH:19]=[C:18]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:15]([C:16]#[N:17])=[C:14]([F:21])[CH:13]=1

参加物

6

反応物 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 24758Sodium hydrideHCID 27569164-Bromo-2,6-difluorobenzonitrile

生成物 1

HCID 585047342-(Benzyloxy)-4-bromo-6-fluorobenzonitrile収率 55.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a 500-mL RBF was added NaH (0.660 g, 27.5 mmol) and THF (100 mL). To this solution was added benzyl alcohol (2.385 mL, 22.94 mmol) in THF slowly via syringe, with external cooling (ice bath) when necessary. After the addition, the reaction mixture was stirred for 1 hour at room temperature. At this time, the mixture was transferred via syringe slowly to a solution of 4-bromo-2,6-difluorobenzonitrile (5 g, 22.94 mmol) in THF at 0° C. The solution was allowed to warm to room temperature and stirred over the weekend. The reaction was poured into water (50 mL), and extracted with EtOAc (3×100 mL). The organic layers were combined and dried over Na2SO4. The dried solution was filtered, and the filtrate was concentrated in vacuo to yield a pale yellow solid which was purified by flash chromatography (gradient elution 0-30% EtOAc in hexanes) to afford the title compound (3.911 g) as a white fluffy solid. 1H NMR (400 MHz, DMSO-d6): δ 5.35 (s, 2H), 7.27-7.66 (m, 7H).

後処理

  1. temperaturewith external cooling (ice bath) when necessary
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. stirringstirred over the weekend
  5. extractionextracted with EtOAc (3×100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationThe dried solution was filtered
  8. concentrationthe filtrate was concentrated in vacuo
  9. customto yield a pale yellow solid which
  10. customwas purified by flash chromatography (gradient elution 0-30% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-08917eb3459e4e19b12ed387de120dc0
出典データセット
uspto-grants-2014_04
特許番号
US08697685B2

反応ノート

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