Sodium Carbonate → tert-butyl 4-(5-(2-phenylpyrimidin-5-yl)-2H-tetrazol-2-yl)piperidine-1-carboxylate

HRID 42309

反応式

HRID 42309 の反応式
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[N:15][NH:16][N:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(O[CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)(C1C=CC(C)=CC=1)(=O)=O.OC1CCN(C(OC(C)(C)C)=O)CC1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[N:15][N:16]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)[N:17]=3)=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 157347131-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidine2 回HCID 592524412-phenyl-5-(1H-tetrazol-5-yl)pyrimidine

生成物 1

HCID 59252463tert-butyl 4-(5-(2-phenylpyrimidin-5-yl)-2H-tetrazol-2-yl)piperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

To a solution consisting of 2-phenyl-5-(2H-tetrazol-5-yl)pyrimidine (25 mg, 0.111 mmol) in DMF (2.0 mL) was added tert-butyl 4-(tosyloxy)piperidine-1-carboxylate (40 mg, 0.111 mmol), synthesized from tert-butyl 4-hydroxypiperidine-1-carboxylate (PCT International Application No. WO 2007/060026), and sodium carbonate (85 mg, 0.45 mmol). The suspension was vigorously stirred for 24 hours and an additional molar equivalent of tert-butyl 4-(tosyloxy)piperidine-1-carboxylate was added and the reaction was heated for another 24 hours at 70° C. After cooling to room temperature, the crude reaction mixture was diluted with ethyl acetate, washed sequentially with 1 M sodium carbonate, 5% citric acid, and brine. After solvent evaporation, the remaining crude solid was dissolved in a minimal amount of dichloromethane and purified by flash silica column chromatography. Elution through a 40-g Analogix® flash silica cartridge with 100% dichloromethane to 2% methanol in dichloromethane provided the title compound as an off-white solid. The solid was further purified by triturating with methanol to afford the title compound as a white solid (15 mg, 33% yield); Rf 0.37 with 95:2 v/v dichloromethane-methanol; melting point 178-180° C.; 1H-NMR (400 MHz; CDCl3) δ 9.47 (s, 2H), 8.52-8.49 (m, 2H), 7.52-7.50 (m, 3H), 4.96-4.95 (m, 2H), 4.23 (bs, 2H), 3.10-2.97 (m, 2H), 2.30-2.21 (m, 4H), 1.48 (s, 9H); MS (ESI+) m/z 408.2 (M+1).

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe crude reaction mixture
  3. washwashed sequentially with 1 M sodium carbonate, 5% citric acid, and brine
  4. customAfter solvent evaporation
  5. dissolutionthe remaining crude solid was dissolved in a minimal amount of dichloromethane
  6. custompurified by flash silica column chromatography
  7. washElution through a 40-g Analogix® flash silica cartridge with 100% dichloromethane to 2% methanol in dichloromethane

出典と根拠

ORDレコード
ord-ef9e59d334a54f419be7aabd304e2c2d
出典データセット
uspto-grants-2013_09
特許番号
US08536185B2

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