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

HRID 1917266

反応式

HRID 1917266 の反応式
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

参加物

12

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8f11950a520e4c4fa8cf10a40a966e78
出典データセット
uspto-grants-2013_12
特許番号
US08618288B2

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