Triethylamine → 1-(2,4-Difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanol

HRID 10219

Reaktionsgleichung

Reaktionsgleichung von HRID 10219
C(N(CC)CC)C.Cl.[F:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH2:19][CH:20]2[CH2:23][NH:22][CH2:21]2)(=[O:18])=[O:17])=[CH:12][CH:11]=1.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]1[CH2:34][O:33]1.Cl([O-])(=O)(=O)=O.[Li+]>C(#N)C.O>[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[CH:32]([OH:33])[CH2:34][N:22]1[CH2:23][CH:20]([CH2:19][S:16]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)(=[O:18])=[O:17])[CH2:21]1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 143729242-(2,4-Difluorophenyl)oxiraneHCID 219783933-{[(4-Fluorophenyl)sulfonyl]methyl}azetidine hydrochlorideHCID 23665649Lithium perchlorate

Produkt 1

HCID 219783771-(2,4-Difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanolAusbeute 34,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

Triethylamine (210 μL, 1.52 mmol) was added to a stirred suspension of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (Example 1 Step 4, 270 mg, 1.02 mmol) in acetonitrile (3 mL) under nitrogen. 2-(2,4-Difluorophenyl)oxirane (WO 99/23083; 1:1 mixture of enantiomers, 238 mg, 1.52 mmol) was added followed by lithium perchlorate (110 mg, 1.03 mmol). The resulting solution was stirred overnight at room temperature. The reaction mixture was poured into water and extracted with dichloromethane (x3). The combined organic layers were washed with water (x3) and brine, dried over MgSO4 and evaporated in vacuo. The residue was triturated with diethyl ether/isohexane then with 5% methanol/ethyl acetate to give 1-(2,4-difluorophenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanol (134 mg, 34%). 1H NMR (500 MHz, CD3OD) δ 7.96–7.92 (2H, m), 7.50–7.46 (1H, m), 7.39–7.33 (2H, m), 6.93–6.91 (1H, m), 6.88–6.84 (1H, m), 3.48 (2H, d, J=7.3 Hz), 3.44–3.38 (2H, m), 2.96–2.88 (2H, m), 2.83–2.75 (1H, m), 2.67–2.61 (2H, m); m/z (ES+) 386 (M+H)+.

Aufarbeitung

  1. extractionextracted with dichloromethane (x3)
  2. washThe combined organic layers were washed with water (x3) and brine
  3. dry with materialdried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was triturated with diethyl ether/isohexane

Quellen und Nachweise

ORD-Eintrag
ord-3a6d532e90c54da2b540f307a77850fe
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094777B2

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