Tetrahydrofuran → 2-Benzyl-4-(tetrahydro-pyran-2-yloxymethyl)-6-p-tolyl-pyrimidine

HRID 1917266

반응식

HRID 1917266 반응식
C1COCC1.CCN(CC)CC.[C:13]1([CH3:22])[CH:18]=[CH:17][C:16]([C:19](Cl)=O)=[CH:15][CH:14]=1.[CH2:23]([O:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][O:28]1)[C:24]#[CH:25].Cl.[C:34]1([CH2:40][C:41]([NH2:43])=[NH:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CO.CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CO>[CH2:40]([C:41]1[N:43]=[C:24]([CH2:23][O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][O:28]2)[CH:25]=[C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:22])=[CH:14][CH:15]=2)[N:42]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

참가 물질

12

반응물 6

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 134054-Methylbenzoyl ChlorideHCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 124155142-Phenylethanimidamide hydrochloride

생성물 1

HCID 666164432-Benzyl-4-(tetrahydro-pyran-2-yloxymethyl)-6-p-tolyl-pyrimidine수율 53.4%

시약·촉매·용매 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 21899815MeOH tetrahydrofuran용매

실험 절차

To a solution of Pd(PPh3)2Cl2 (0.285 g, 0.41 mmol) and CuI in THF (50 mL) (0.148 g, 0.777 mmol) was added Et3N (1.5 mL, 11.0 mmol), p-toluoyl chloride (1.3 mL, 10.0 mmol) and tetrahydro-2-(2-propynyloxy)-2H-pyran (1.4 mL, 10.0 mmol). After stirring for 2.5 h, a solution of 2-phenylacetamidine hydrochloride (2.0 g, 11.7 mmol) in THF/MeOH (1:1, 10 mL) was added followed by additional MeOH (5 mL) and Na2CO3 (3.2 g, 30.0 mmol). The reaction mixture was heated at reflux for 15 h, cooled to rt, diluted with Et2O and filtered through a small pad of diatomaceous earth. The filtrate was concentrated and purified via SiO2 chromatography (10-45% EtOAc/hexanes) to give 2.0 g (53%) of the title compound. 1H NMR (CDCl3): 8.02-8.00 (m, 2H), 7.68 (s, 1H), 7.46-7.44 (m, 2H), 7.30-7.27 (m, 4H), 7.21-7.19 (m, 1H), 4.87 (d, J=14.7, 1H), 4.77 (t, J=3.5, 1H), 4.62 (d, J=15.1, 1H), 4.31 (s, 2H), 3.91-3.86 (m, 1H), 3.57-3.52 (m, 1H), 2.41 (s, 3H), 1.96-1.87 (m, 1H), 1.84-1.72 (m, 2H), 1.66-1.55 (m, 3H).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 15 h
  3. filtrationfiltered through a small pad of diatomaceous earth
  4. concentrationThe filtrate was concentrated
  5. custompurified via SiO2 chromatography (10-45% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-8f11950a520e4c4fa8cf10a40a966e78
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618288B2

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