Probucol → HCID 86602765, compound

HRID 916993Notes

Reaction equation

HRID 916993 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].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:55][C:56]1([CH3:65])[O:60][C@@H:59]([CH2:61][CH2:62][CH2:63]O)[CH2:58][O:57]1.CCOC(/N=N/C(OCC)=O)=O>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][CH2:63][CH2:62][CH2:61][C@@H:59]3[CH2:58][O:57][C:56]([CH3:65])([CH3:55])[O:60]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 27338903-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]propan-1-olHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 86602765HCID 86602765, compoundYield 35.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of probucol (2.93 g, 5.7 mmole) in 100 ml of THF were added Ph3P (1.63 g, 6.2 mmole) and 3-[2,2-dimethyl-1,3-dioxolane-4(S)-yl]-propanol (1.0 g, 6.2 mmole). The mixture was cooled to 0° C. with an ice bath, and DEAD (1.1 g, 6.2 mmol) was then added dropwise under nitrogen. The mixture was stirred overnight while allowed to warm to room temperature and then heated to reflux. The reaction mixture was cooled and concentrated to an oily residue when HPLC and TLC showed that the new peak ceased to grow. Chromatography on silica gel with gradient solvent from hexanes to 25% EtOAc in hexanes to afford 1.3 g (35.1%) 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[3-(2,2-dimethyl-[1,3]dioxolan-4(R)-yl)-propoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)phenol as a white solid. 1H-NMR (CDCl3) δ 7.53 (s, 2H), 7.45 (s, 2H), 5.37(s, 1H), 4.05–4.17 (m, 2H), 3.71–3.77 (m, 2H), 3.35 (t, J=2.5 Hz, 1H), 1.90–2.00 (m, 2H), 1.63–1.73 (m, 2H), 1.42–1.46 (m, 42H). MS m/z: 676.4429 ([M+NH4]+, 25%)

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated to reflux
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated to an oily residue when HPLC and TLC

Sources & evidence

ORD record
ord-37b5cffa09e141eba1a68bab63416ffa
Source dataset
uspto-grants-2007_09
Patent number
US07271274B2

Reaction notes

Loading…