Methyl benzenesulfonate → 1-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one

HRID 17984노트

반응식

HRID 17984 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1(S(OC)(=O)=O)C=CC=CC=1>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]=[CH:8][C:7]1=[O:12]

참가 물질

6

반응물 3

HCID 6630Methyl benzenesulfonateHCID 2733832Lithium HexamethyldisilazideHCID 669976831-(3-Chloro-4-fluorobenzyl)piperidin-2-one

생성물 1

HCID 594556041-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
-20 °C

실험 절차

To a cold (−20° C.) solution of 1-(3-chloro-4-fluorobenzyl)piperidin-2-one (340 g, 1.41 mol) in anhydrous tetrahydrofuran (5 L) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide (3.09 L, 3.09 mol; 1M in TIE) was added over a period of 40 minutes with the temperature of the reaction maintained at −20° C. After the addition was complete, the reaction mixture was stirred at −20° C. for one hour. Methyl benzene sulfonate (231 mL, 1.69 mol) was added to the reaction mixture over a period of 30 minutes. The reaction mixture was stirred at −20° C. for 30 minutes. The product mixture was diluted with ethyl acetate (4 L) and washed with water (four times; 2 L each time). The organic extract was concentrated under vacuum. The residue was dissolved in toluene (4 L), treated with solid sodium carbonate (500 g), and heated at 100° C. for one hour. The product mixture was diluted with ethyl acetate (4 L) and washed with water (4 times; 2 L each). The organic extract was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a gradient of 0-60% EtOAc in heptane. Collection and concentration of appropriate fractions provide the title compound as oil.

후처리

  1. additionAfter the addition
  2. stirringThe reaction mixture was stirred at −20° C. for 30 minutes
  3. washwashed with water (four times; 2 L each time)
  4. extractionThe organic extract
  5. concentrationwas concentrated under vacuum
  6. dissolutionThe residue was dissolved in toluene (4 L)
  7. additiontreated with solid sodium carbonate (500 g)
  8. temperatureheated at 100° C. for one hour
  9. additionThe product mixture was diluted with ethyl acetate (4 L)
  10. washwashed with water (4 times; 2 L each)
  11. extractionThe organic extract
  12. concentrationwas concentrated under vacuum
  13. customCollection and concentration of appropriate fractions

출처 및 근거

ORD 기록
ord-00911e535774408c95edef86f439d8e1
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741315B2

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