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 916991노트

반응식

HRID 916991 반응식
[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]

참가 물질

6

반응물 4

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

생성물 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)-phenol수율 28.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c37f6246c1a14ba381796eed33d8cc9d
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07271274B2

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