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 916991Notes

Reaction equation

HRID 916991 reaction equation
[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]

Participants

6

Reactant 4

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

Product 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)-phenolYield 28.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-c37f6246c1a14ba381796eed33d8cc9d
Source dataset
uspto-grants-2007_09
Patent number
US07271274B2

Reaction notes

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