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

HRID 916985

Reaktionsgleichung

Reaktionsgleichung von HRID 916985
[CH3:1][C:2]([C:5]1[CH:6]=[C:7]([S:16][C:17]([S:20][C:21]2[CH:26]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24]([OH:31])=[C:23]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:22]=2)([CH3:19])[CH3:18])[CH:8]=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:10]=1[OH:11])([CH3:4])[CH3:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[CH2:67]([O:69][CH:70]1[O:74][C@@H:73]([CH2:75]O)[C@H:72]([CH2:77][OH:78])[O:71]1)[CH3:68]>C1COCC1>[C:12]([C:9]1[CH:8]=[C:7]([S:16][C:17]([S:20][C:21]2[CH:22]=[C:23]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:24]([O:31][CH2:75][C@H:73]3[C@H:72]([CH2:77][OH:78])[O:71][CH:70]([O:69][CH2:67][CH3:68])[O:74]3)=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:26]=2)([CH3:18])[CH3:19])[CH:6]=[C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[C:10]=1[OH:11])([CH3:13])([CH3:14])[CH3:15]

Komponenten

6

Edukt 4

HCID 4912ProbucolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 12142789[(4S,5S)-2-ethoxy-5-(hydroxymethyl)-1,3-dioxolan-4-yl]methanol

Produkt 1

HCID 112853662,6-di-tert-butyl-4-{1-[3,5-di-tert-butyl-4-(2-ethoxy-5(S)-hydroxymethyl-[1,3]dioxolan-4(S)-yl-methoxy)-phenylsulfanyl]-1-methyl-ethylsulfanyl}-phenolAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of probucol (5.16 g, 10 mmol) in THF (20 mL) cooled to 0° C. were added triphenylphosphine (1.3 g, 5 mmol), diethyl azodicarboxylate (0.8 mL g, 5 mmol) and 2-ethoxy-1,3-dioxolane-4(S),5(S)-dimethanol (0.89 g, 5 mmol; Nicolaou, K. C. et al.: J. Org. Chem. 1985, 50, 1440–1456). The resultant mixture was stirred at reflux for 3 hours and then evaporated. Silica gel chromatography (hexanes/ethyl acetate 4:1) gave 2,6-di-tert-butyl-4-{1-[3,5-di-tert-butyl-4-(2-ethoxy-5(S)-hydroxymethyl[1,3]dioxolan-4(S)-yl-methoxy)-phenylsulfanyl]-1-methyl-ethylsulfanyl}-phenol in three parts: diasteroisomer A (0.36 g), diastereoisomer B (0.22 g) and a mixture of the two (0.72 g) all as viscous residues (total yield: 39%). Diastereoisomer A: 1H-NMR (CDCl3) δ 7.56 (s, 2H, Ph-H), 7.44 (s, 2H, Ph-H), 5.89 [s, 1H, CH(O) 3], 5.37 (s, 1H, PhOH), 4.7{tilde over (3)}4.81 (m, 1H, PhOCH2CH), 4.1{tilde over (9)}4.25 (m, 1H, CHCH2OH), 3.8{tilde over (0)}4.01 (m, 3H, CH2O), 3.6{tilde over (2)}3.96 (m, 3H, CH2O), 2.80 (dd, J=9, 3, 1H, OH), 1.45 (s, 6H, S,S′-isopropylidene), 1.44 (s, 18H, tert-butyls), 1.43 (s, 18H, tert-butyls), 1.25 (t, 3H, OCH2CH3). Diasteroisomer B: 1H-NMR (CDCl3) δ 7.56 (s, 2H, Ph-H), 7.44 (s, 2H, Ph-H), 5.92 [s, 1H, CH(O) 3], 5.36 (s, 1H, PhOH), 4.5{tilde over (0)}4.59 (m, 1H, PhOCH2CH), 4.1{tilde over (3)}4.30 (m, 3H, CHCH2OH, CH2O), 3.8{tilde over (9)}4.00 (m, 3H, CH2O), 3.61 (quad, J=7, 2H, OCH2CH3), 1.86 (dd, J=6, 8, 1H, OH), 1.4{tilde over (1)}1.46 (m, 42H, S,S′-isopropylidene, tert-butyls), 1.21 (t, 3H, OCH2CH3).

Aufarbeitung

  1. temperatureat reflux for 3 hours
  2. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-331d8fc4b8f94bdc9517eff86157059e
Quelldatensatz
uspto-grants-2007_09
Patentnummer
US07271274B2

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