HCID 25207258, Verbindung → HCID 70873244, Verbindung

HRID 1022467

Reaktionsgleichung

Reaktionsgleichung von HRID 1022467
[OH:1][C@H:2]1[C@H:9]2[C@H:5]([O:6][C:7]([CH3:11])([CH3:10])[O:8]2)[O:4][C@H:3]1[C:12](N1CCOCC1)=[O:13].C([Mg]Cl)(C)C.[Br:25][C:26]1[CH:42]=[CH:41][C:40](I)=[CH:39][C:27]=1[CH2:28][C:29]1[CH:38]=[CH:37][C:32]2[O:33][CH2:34][CH2:35][O:36][C:31]=2[CH:30]=1>C1COCC1>[Br:25][C:26]1[CH:42]=[CH:41][C:40]([C:12]([C@@H:3]2[O:4][C@H:5]3[O:6][C:7]([CH3:10])([CH3:11])[O:8][C@H:9]3[C@@H:2]2[OH:1])=[O:13])=[CH:39][C:27]=1[CH2:28][C:29]1[CH:38]=[CH:37][C:32]2[O:33][CH2:34][CH2:35][O:36][C:31]=2[CH:30]=1

Komponenten

5

Edukt 3

HCID 25207258HCID 25207258, VerbindungHCID 583408306-(2-Bromo-5-iodobenzyl)-2,3-dihydrobenzo[b][1,4]dioxineHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 70873244HCID 70873244, VerbindungAusbeute 6,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Step-V: To a cooled solution of ((3aS,5R,6S,6aS)-6-Hydroxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-morpholin-4-yl-methanone (11.05 g, 256 mmol) in THF (200 ml) was added 2.0 M solution of isopropylmagnesium chloride (12.78 ml, 256 mmol) under stirring at 0° C. and stirred for additional 1.5 h. To this was added a solution of 6-(2-bromo-5-iodo-benzyl)-2,3-dihydro-benzo[1,4]dioxine (4.0 g, 146 mmol) in THF (50 ml) at 0° C. and then stirred at room temperature for 2 h. The reaction mixture was quenched by the addition of aqueous saturated ammonium chloride solution and extracted with ethyl acetate (200 ml×3). Combined organic layers were washed with brine (500 ml), dried over sodium sulfate, concentrated and purified by silica gel column chromatography to give 4.7 g of [4-bromo-3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-phenyl]-((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-methanone. 1H NMR (400 MHz, CDCl3): δ 1.35 (s, 3H), 1.53 (s, 3H), 2.92 (d, J=4.0 Hz, 1H), 4.04 (d, J=3.6 Hz, 2H), 4.23 (s, 4H), 4.54 (br s, 1H), 4.56 (d, J=3.6 Hz, 1H), 5.21 (d, J=2.8 Hz, 1H), 6.05 (d, J=3.2 Hz, 1H), 6.67 (s, 2H), 6.79 (d, J=9.2 Hz, 1H), 7.68 (d, J=9.2 Hz, 1H), 7.75-7.77 (m, 2H). MS (ES) m/z 490.7 (M+1).

Aufarbeitung

  1. stirringstirred for additional 1.5 h
  2. stirringstirred at room temperature for 2 h
  3. customThe reaction mixture was quenched by the addition of aqueous saturated ammonium chloride solution
  4. extractionextracted with ethyl acetate (200 ml×3)
  5. washCombined organic layers were washed with brine (500 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. custompurified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5591597e4bfa49cba49d27cef7eab6c1
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722633B2

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