Probucol → HCID 86602766, compound

HRID 916997Notes

Reaction equation

HRID 916997 reaction equation
[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].[CH2:36]([O:38][CH:39]1[O:43][CH:42]([CH2:44][CH2:45]O)[CH:41]([CH2:47][CH2:48][OH:49])[O:40]1)[CH3:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[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][CH2:45][CH2:44][CH:42]3[CH:41]([CH2:47][CH2:48][OH:49])[O:40][CH:39]([O:38][CH2:36][CH3:37])[O:43]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]

Participants

6

Reactant 4

HCID 4912ProbucolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 69494660HCID 69494660, compound

Product 1

HCID 86602766HCID 86602766, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of probucol (19.0 g, 37 mmol) and 2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxolan-4-yl]-ethanol (Ex-14C, 7.6 g, 37 mmol) in tetrahydrofuran (160 mL) was added triphenylphosphine (10.6 g, 41 mmol) and the resulting mixture was cooled to 0° C. Diethyl azodicarboxylate (7.1 g, 41 mmol) was then added dropwise, stirred at 0° C. for 30 min, and allowed to warm to rt. The solution was ultimately heated to 65° C. and stirred for an additional 18 h for the reaction to complete. The reaction mixture was concentrated under reduced pressure to an orange viscous oil and titurated with hexanes and the resulting slurry was stirred at rt for 30 min. The solution was filtered to remove the triphenylphosphine oxide and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel chromatography (10% ethyl acetate/hexanes with a gradual increase to 30% ethyl acetate/hexanes) to afford 7.4 g (30%) of 2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-{2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxolan-4-yl]-ethoxy}-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenol as a white solid. 1H-NMR (300 MHz, CDCl3) δ7.53 (s, 2H), 7.45 (s, 2H), 5.81 (s. 1H), 5.36 (s, 1H), 4.09–4.19 (m, 2H), 3.84–3.92 (m, 4H), 3.59 (q, 2H, J=6.8 Hz), 2.17–2.19 (m, 2H), 2.02–2.05 (m, 1H), 1.86–1.96 (m, 2H), 1.42–1.44 (m, 42H), 1.19–1.24 (m, 3H). HRMS (ESI) calcd for C40H64O6S2 (M+K), 727.4042; found, 727.4050. Anal. calcd. for C40H64O6S2: C, 66.62, H, 9.55, S, 8.68; found: C, 66.65, H, 9.35, S, 9.01.

Workup

  1. temperatureto warm to rt
  2. temperatureThe solution was ultimately heated to 65° C.
  3. stirringstirred for an additional 18 h for the reaction
  4. concentrationThe reaction mixture was concentrated under reduced pressure to an orange viscous oil
  5. stirringthe resulting slurry was stirred at rt for 30 min
  6. filtrationThe solution was filtered
  7. customto remove the triphenylphosphine oxide
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. temperaturea gradual increase to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-92a85f517aac4534b9a9dc16f783c701
Source dataset
uspto-grants-2007_09
Patent number
US07271274B2

Reaction notes

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