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Ammonium Chloride → 2-(4-Tert-butyl-2-1,3-dioxinan-2-yl-6-fluoro-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole

HRID 1185020
ノート
印刷プレビュー

反応式

HRID 1185020 の反応式
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][CH2:13][C:14]([CH3:17])([CH3:16])[N:15]=2)=[C:7]([CH:18]2[O:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:39])(=O)=O)=CC=1.[NH4+].[Cl-]>C1COCC1.CCCCCC>[C:1]([C:5]1[CH:10]=[C:9]([F:39])[C:8]([C:11]2[O:12][CH2:13][C:14]([CH3:17])([CH3:16])[N:15]=2)=[C:7]([CH:18]2[O:23][CH2:22][CH2:21][CH2:20][O:19]2)[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 594738142-(4-(tert-Butyl)-2-(1,3-dioxan-2-yl)phenyl)-4,4-dimethyl-4,5-dihydrooxazoleHCID 178418339Butyllithium

生成物 1

HCID 594737622-(4-Tert-butyl-2-1,3-dioxinan-2-yl-6-fluoro-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole収率 33.1%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回
HCID 8058Hexane溶媒

反応条件

温度
-17 °C

実験手順

To a solution of 101e (20 g, 63 mmol) in anhydrous THF (400 mL) was added 2.4 M solution of n-butyllithium in hexane (65 mL) at −78° C. under N2 atmosphere. The clear yellow solution was stirred at −17° C. for 3 hr, when it showed a deep red-orange color. The reaction solution was re-cooled to −78° C., stirred rapidly and a solution of N-fluorobenzenesulfonimide (29 g, 92 mmol) in anhydrous THF (100 mL) was added in dropwise over 10 min. The reaction mixture was stirred at −78° C. for 5 min, −20° C. for 30 min, then room temperature for 1 h. The reaction mixture was poured into 150 mL of 50% aqueous NH4Cl and extracted with 300 mL of EtOAc. The separated organic phase was washed with 150 mL of water and 150 mL of brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a residue which was purified by silica gel chromatography using EtOAc/CH2Cl2=1:5 as eluent to afford 101f (7 g, 33%) as yellow solid. LCMS (ESI) m/z 336 (M+H)+. 1HNMR (300 MHz, CDCl3) δ 7.53 (d, J=1.6 Hz, 1H), 7.08 (dd, J=2.0, 12.0 Hz, 1H), 5.90 (s, 1H), 4.24 (dd, J=5.2, 10.8 Hz, 2H), 4.06 (s, 2H), 3.98-3.91 (m, 2H), 2.26-2.19 (m, 1H), 1.45-1.42 (m, 1H), 1.42 (s, 6H), 1.30 (s, 9H).

後処理

  1. temperatureThe reaction solution was re-cooled to −78° C.
  2. stirringstirred rapidly
  3. stirringThe reaction mixture was stirred at −78° C. for 5 min, −20° C. for 30 min
  4. waitroom temperature for 1 h
  5. extractionextracted with 300 mL of EtOAc
  6. washThe separated organic phase was washed with 150 mL of water and 150 mL of brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a residue which
  11. customwas purified by silica gel chromatography

出典と根拠

ORDレコード
ord-fa5df6c844c145c1a2e3e503a4d6b23e
出典データセット
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08669251B2

反応ノート

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