Sodium Chloride → 3(S)-Isopropyl-5(S)-{1(S)-azido4(R,S)-hydroxy-3(S)-isopropyl-4-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-butyl}-tetrahydrofuran-2-one

HRID 725663

反応式

HRID 725663 の反応式
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][C:9]=1[O:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20].CN1CCOCC1.[Br-].[Mg+2].[Br-].[Mg].BrCCBr.[CH:36]([C@@H:39]1[CH2:43][C@@H:42]([C@@H:44]([N:52]=[N+:53]=[N-:54])[CH2:45][C@@H:46]([CH:49]([CH3:51])[CH3:50])[CH:47]=[O:48])[O:41][C:40]1=[O:55])([CH3:38])[CH3:37].[Cl-].[NH4+].[Cl-].[Na+]>O1CCCC1>[CH:36]([C@@H:39]1[CH2:43][C@@H:42]([C@@H:44]([N:52]=[N+:53]=[N-:54])[CH2:45][C@@H:46]([CH:49]([CH3:50])[CH3:51])[CH:47]([OH:48])[C:11]2[CH:12]=[CH:13][C:8]([O:7][CH3:6])=[C:9]([O:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])[CH:10]=2)[O:41][C:40]1=[O:55])([CH3:37])[CH3:38]

参加物

11

反応物 9

HCID 5234Sodium ChlorideHCID 78391,2-DibromoethaneHCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 82241Magnesium BromideHCID 5462224MagnesiumHCID 214587114-Bromo-1-methoxy-2-(3-methoxypropoxy)benzeneHCID 22865773(S)-2-[(S)-2-azido-2-((2S,4S)-4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-3-methyl-butyraldehydeHCID 178418339Butyllithium

生成物 1

HCID 1222222643(S)-Isopropyl-5(S)-{1(S)-azido4(R,S)-hydroxy-3(S)-isopropyl-4-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-butyl}-tetrahydrofuran-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
-75 °C

実験手順

45.1 ml of a 1N n-butyllithium solution (in hexane) are added dropwise at -75° C. to a mixture of 12.1 g of 4-methoxy-3-(3-methoxypropyloxy)-bromobenzene and 9.7 ml of 4-methylmorpholine in 75 ml of tetrahydrofuran. The reaction mixture is stirred for a further 20 minutes at -75° C. and then, at from -75° C. to -60° C., a suspension of magnesium bromide in tetrahydrofuran (freshly prepared from 1.6 g of magnesium powder and 5.7 ml of 1,2-dibromoethane in 150 ml of tetrahydrofuran) is added. The reaction mixture is stirred for a further 30 minutes and then, at -75° C. (2, a solution of 8.84 g of 3(S)-isopropyl-5(S)-[1(S)-azido-3(S)-isopropyl-4-oxobutyl]-tetrahydrofuran-2-one in 75 ml of tetrahydrofuran is added. The reaction mixture is then stirred for 15 minutes at -75° C. and subsequently 70 ml of saturated ammonium chloride solution are added. The reaction mixture is then poured into 180 ml of saturated sodium chloride solution:water (1:1) and extracted with ethyl acetate (2×360 ml). The organic phases are dried over magnesium sulfate and concentrated by evaporation. The title compound is obtained by purifying the residue by FC (240 g of silica gel, ethyl acetate/hexane=1:2)=Rf (ethyl acetate/hexane=1:2)=0.16; HPLC Rt =18.53 and 19.49 minutes (diastereoisomeric mixture).

後処理

  1. additionis added
  2. stirringThe reaction mixture is stirred for a further 30 minutes
  3. stirringThe reaction mixture is then stirred for 15 minutes at -75° C.
  4. extractionwater (1:1) and extracted with ethyl acetate (2×360 ml)
  5. dry with materialThe organic phases are dried over magnesium sulfate
  6. concentrationconcentrated by evaporation

出典と根拠

ORDレコード
ord-79b54c99c11c424995dffdccc99cf15d
出典データセット
uspto-grants-1998_01
特許番号
US05705658

関連ノート

読み込み中…