Iodine → 3(S)-Isopropyl-5(S)-{1 (S)-azido-3(S)-isopropyl-4(R,S)-hydroxy-4-[4-methoxy-3-(2-methoxymethoxyethyl)-phenyl]-butyl}-tetrahydrofuran-2-one

HRID 725614

反応式

HRID 725614 の反応式
II.[Mg].Br[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([CH2:13][CH2:14][O:15][CH2:16][O:17][CH3:18])[CH:6]=1.[CH:19]([C@@H:22]1[CH2:26][C@@H:25]([C@@H:27]([N:35]=[N+:36]=[N-:37])[CH2:28][C@@H:29]([CH:32]([CH3:34])[CH3:33])[CH:30]=[O:31])[O:24][C:23]1=[O:38])([CH3:21])[CH3:20].[Cl-].[NH4+]>O1CCCC1.BrCCBr.O.C(O)(=O)C>[CH:19]([C@@H:22]1[CH2:26][C@@H:25]([C@@H:27]([N:35]=[N+:36]=[N-:37])[CH2:28][C@@H:29]([CH:32]([CH3:33])[CH3:34])[CH:30]([OH:31])[C:5]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([CH2:13][CH2:14][O:15][CH2:16][O:17][CH3:18])[CH:6]=2)[O:24][C:23]1=[O:38])([CH3:20])[CH3:21]

参加物

10

反応物 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 214585954-Bromo-2-(2-methoxymethoxyethyl)-anisoleHCID 22865773(S)-2-[(S)-2-azido-2-((2S,4S)-4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-3-methyl-butyraldehyde

生成物 1

HCID 574848163(S)-Isopropyl-5(S)-{1 (S)-azido-3(S)-isopropyl-4(R,S)-hydroxy-4-[4-methoxy-3-(2-methoxymethoxyethyl)-phenyl]-butyl}-tetrahydrofuran-2-one

試薬・触媒・溶媒 4

HCID 78391,2-Dibromoethane触媒HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒4 回

実験手順

Several iodine crystals are added to a suspension of 763 mg of magnesium chips in 0.5 ml of tetrahydrofuran, and the mixture is activated in an ultrasound bath for 30 minutes. Then 4 drops of 1,2-dibromoethane and then a solution of 8.64 g of 4-bromo-2-(2-methoxymethoxyethyl)-anisole in 30 ml of tetrahydrofuran are added dropwise in such a manner that the reaction mixture boils under reflux. When the addition is complete, the mixture is maintained under reflux for a further one hour. The reaction mixture is then added dropwise within a period of 45 minutes, with stirring, to a solution, cooled to -75° C., of 2.85 g of 3(S)-isopropyl-5(S)-[1(S)-azido-3(S)-isopropyl-4-oxobutyl]-tetrahydrofuran-2-one in 20 ml of tetrahydrofuran. The reaction mixture is stirred for a further 150 minutes at -75° C., and there are then added thereto, at the same temperature, a solution of 1.4 ml of glacial acetic acid in 1 ml of tetrahydrofuran and then 25 ml of saturated ammonium chloride solution. The reaction mixture is then brought to room temperature, poured onto 60 ml of water and extracted three times with 100 ml of ethyl acetate. The organic phases are washed with 50 ml of saturated sodium chloride solution, combined, dried over magnesium sulfate and concentrated by evaporation. Purification of the residue by means of FC (400 g of silica gel, hexane/ethyl acetate=8:2) yields the title compound: Rf (hexane/ethyl acetate=7:3)=0.25; HPLC Rt =48.10 and 50.29 minutes (diastereoisomeric mixture).

後処理

  1. temperatureunder reflux
  2. additionWhen the addition
  3. temperaturethe mixture is maintained
  4. temperatureunder reflux for a further one hour
  5. additionThe reaction mixture is then added dropwise within a period of 45 minutes
  6. stirringThe reaction mixture is stirred for a further 150 minutes at -75° C.
  7. additionthere are then added
  8. customis then brought to room temperature
  9. extractionextracted three times with 100 ml of ethyl acetate
  10. washThe organic phases are washed with 50 ml of saturated sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated by evaporation
  13. customPurification of the residue by means of FC (400 g of silica gel, hexane/ethyl acetate=8:2)

出典と根拠

ORDレコード
ord-dcb4f3d41cfe47eab31e847f3f0a6ae7
出典データセット
uspto-grants-1998_01
特許番号
US05705658

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