Probucol → 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenol

HRID 916991Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 916991
[CH3:1][C:2]1([CH3:11])[O:6][C@@H:5]([CH2:7][CH2:8][OH:9])[C:4](=O)[O:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:31][C:32]([C:35]1[CH:36]=[C:37]([S:46][C:47]([S:50][C:51]2[CH:56]=[C:55]([C:57]([CH3:60])([CH3:59])[CH3:58])[C:54]([OH:61])=[C:53]([C:62]([CH3:65])([CH3:64])[CH3:63])[CH:52]=2)([CH3:49])[CH3:48])[CH:38]=[C:39]([C:42]([CH3:45])([CH3:44])[CH3:43])[C:40]=1O)([CH3:34])[CH3:33].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:57]([C:55]1[CH:56]=[C:51]([S:50][C:47]([S:46][C:37]2[CH:36]=[C:35]([C:32]([CH3:34])([CH3:33])[CH3:31])[C:40]([O:9][CH2:8][CH2:7][C@H:5]3[CH2:4][O:3][C:2]([CH3:11])([CH3:1])[O:6]3)=[C:39]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=2)([CH3:49])[CH3:48])[CH:52]=[C:53]([C:62]([CH3:65])([CH3:64])[CH3:63])[C:54]=1[OH:61])([CH3:60])([CH3:59])[CH3:58]

Komponenten

6

Edukt 4

HCID 4912ProbucolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10975778(S)-5-(2-Hydroxyethyl)-2,2-dimethyl-1,3-dioxolan-4-one

Produkt 1

HCID 866027642,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenolAusbeute 28,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A 1 L round bottom flask equipped with a nitrogen adapter, temperature probe and addition funnel was charged with 9.3 g (58 mmol, 1.3 eq) of (s)-(+)-2,2-dimethyl-5-oxo-1,3-dioxolane-4-ethanol (Ex-10A), 500 mL of anhydrous THF, 25.6 g (98.3 mmol, 2.2 eq) of triphenylphosphine and 23.1 g (44.7 mmol, 1 eq) of probucol. The reaction mixture was cooled to 0° C. with an ice bath, 14.0 mL (89.4 mmol, 2.0 eq) of diethyl azodicarboxylate was charged to the addition funnel and then added dropwise to the reaction mixture. The dark reaction mixture was warmed to ambient temperature and stirred for 18 hours. The reaction mixture concentrated under reduced pressure and the residue was purified by silica gel chromatography (2% EtOAc/hexanes gradient to 5% EtOAc/hexanes) to yield 8.2 g of 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenol as a white solid, mp 44–46° C. 1H NMR (300 MHz, CDCl3) δ: 7.56 (s, 2H), 7.47 (s, 2H), 5.38 (s, 1H), 4.61 (dd, J=9.17 and 3.75 Hz, 1H), 3.92–4.00 (m, 1H), 3.79–3.87 (m, 1H), 2.50–2.61 (m, 1H), 2.15–2.27 (m, 1H), 1.47 (s, 6H), 1.46 (s, 18H), 1.45 (s, 18H). HRMS (EI+) m/z+Na: calc. 681.3623; found 681.3619.

Aufarbeitung

  1. customA 1 L round bottom flask equipped with a nitrogen adapter
  2. additiontemperature probe and addition funnel
  3. additionadded dropwise to the reaction mixture
  4. customThe dark reaction mixture
  5. temperaturewas warmed to ambient temperature
  6. concentrationThe reaction mixture concentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (2% EtOAc/hexanes gradient to 5% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c37f6246c1a14ba381796eed33d8cc9d
Quelldatensatz
uspto-grants-2007_09
Patentnummer
US07271274B2

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