Triethylamine → 4-(5-Phenylethynyl-pyridin-2-ylmethyl)-morpholin-3-one

HRID 1020184노트

반응식

HRID 1020184 반응식
[C:1]1([C:7]#[C:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15]O)=[N:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(Cl)(=O)=O.C(N(CC)CC)C.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][C:30]1=[O:35].[H-].[Na+].C([O-])(O)=O.[Na+]>ClCCl.CN(C=O)C>[C:1]1([C:7]#[C:8][C:9]2[CH:10]=[CH:11][C:12]([CH2:15][N:29]3[CH2:34][CH2:33][O:32][CH2:31][C:30]3=[O:35])=[N:13][CH:14]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

참가 물질

9

반응물 6

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 669533-MorpholinoneHCID 516892Sodium BicarbonateHCID 57517077(5-Phenylethynyl-pyridin-2-yl)-methanol

생성물 1

HCID 529171904-(5-Phenylethynyl-pyridin-2-ylmethyl)-morpholin-3-one수율 54%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

(0.20 g, 0.96 mmol) (5-Phenylethynyl-pyridin-2-yl)-methanol (example 31, step 1) was dissolved in dichloromethane (5 ml) and methanesulfonyl chloride (75 μl, 0.96 mmol, 1.0 equiv.) and triethylamine (270 μl, 1.91 mmol, 2 equiv.) were added at 0-5° C. The mixture was stirred for 1 hour at room temperature. The reaction mixture was evaporated, dissolved in 2 ml DMF and added to a suspension of morpholin-3-one (97 mg, 0.96 mmol, 1.0 equiv.) previously treated with sodium hydride (60%) (69 mg, 1.43 mmol, 1.5 equiv.) in 2 ml DMF. The mixture was stirred for 3 hours at room temperature. The reaction mixture was treated with sat. NaHCO3 solution and extracted twice with EtOAc. The organic layers were extracted with water, dried over sodium sulfate and evaporated to dryness. The crude material was purified by flash chromatography on silica gel (20 gr, ethyl acetate/heptane gradient, 0:100 to 0:100). The desired 4-(5-phenylethynyl-pyridin-2-ylmethyl)-morpholin-3-one (150 mg, 54% yield) was obtained as a light brown solid, MS: m/e=293.1 (M+H+).

후처리

  1. customThe reaction mixture was evaporated
  2. dissolutiondissolved in 2 ml DMF
  3. stirringThe mixture was stirred for 3 hours at room temperature
  4. extractionextracted twice with EtOAc
  5. extractionThe organic layers were extracted with water
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness
  8. customThe crude material was purified by flash chromatography on silica gel (20 gr, ethyl acetate/heptane gradient, 0:100 to 0:100)

출처 및 근거

ORD 기록
ord-032d8dde2d2d4423ba476873324ba9b9
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716316B2

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