p-Bromochlorobenzene → (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone

HRID 2396998ノート

反応式

HRID 2396998 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[Mg].[O:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[O:16][C@H:17]([CH3:26])[C:18](N1CCOCC1)=[O:19].[Cl-].[NH4+]>O1CCCC1.O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:18](=[O:19])[C@H:17]([O:16][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][O:10]2)[CH3:26])=[CH:3][CH:4]=1

参加物

7

反応物 4

HCID 7806p-Bromochlorobenzene2 回HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 10977653(2R)-1-morpholino-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

生成物 1

HCID 10445767(2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone収率 235.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a solution of 1-bromo-4-chlorobenzene (20 g) in tetrahydrofuran (260 ml) was added magnesium (turnings, 7.47 g). The mixture was vigorously stirred at room temperature. When the temperature of the mixture reached 40° C., the reaction vessel was cooled in a water bath. A solution of 1-bromo-4-chlorobenzene (38.9 g) in tetrahydrofuran (90 ml), was added dropwise to the mixture at 34°-40° C., followed by stirring for an hour at 30° C. To the mixture was added dropwise a solution of 4-[(2R)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl]morpholine (60 g) in tetrahydrofuran (60 ml) over the period of 15 minutes at 0° C. The mixture was stirred for 3 hours at room temperature. To the reaction mixture were added a saturated aqueous ammonium chloride solution (120 ml) and water (100 ml). The mixture was extracted with ethyl acetate (500 ml). The organic layer was washed with water, dried over magnesium sulfate and distilled under reduced pressure. The residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1) to give (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (66 g) as a pale yellow oily substance.

後処理

  1. customreached 40° C.
  2. temperaturethe reaction vessel was cooled in a water bath
  3. stirringby stirring for an hour at 30° C
  4. stirringThe mixture was stirred for 3 hours at room temperature
  5. extractionThe mixture was extracted with ethyl acetate (500 ml)
  6. washThe organic layer was washed with water
  7. dry with materialdried over magnesium sulfate
  8. distillationdistilled under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1)

出典と根拠

ORDレコード
ord-781c3009ea624f0f8ef7387bd1a0707d
出典データセット
uspto-grants-1996_02
特許番号
US05495024

反応ノート

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