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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
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1185020
[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]
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Komponenten

7

Edukt 4

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

Produkt 1

HCID 594737622-(4-Tert-butyl-2-1,3-dioxinan-2-yl-6-fluoro-phenyl)-4,4-dimethyl-4,5-dihydro-oxazoleAusbeute 33,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-17 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-fa5df6c844c145c1a2e3e503a4d6b23e
Quelldatensatz
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08669251B2

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