1,2-Dibromoethane → 3(S)-Isopropyl-5(S)-{1(S)-azido-3(S)-isopropyl-4(R,S)-hydroxy-4-(4-(3-benzyloxy-propyloxy)-3-(3-methoxypropyloxy)phenyl]-butyl}-tetrahydrofuran-2-one

HRID 725621

Reaktionsgleichung

Reaktionsgleichung von HRID 725621
C([Li])CCC.[CH2:6]([O:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][C:19]=1[O:25][CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Br-].[Mg+2].[Br-].[Mg].BrCCBr.[CH:39]([C@@H:42]1[CH2:46][C@@H:45]([C@@H:47]([N:55]=[N+:56]=[N-:57])[CH2:48][C@@H:49]([CH:52]([CH3:54])[CH3:53])[CH:50]=[O:51])[O:44][C:43]1=[O:58])([CH3:41])[CH3:40].[Cl-].[NH4+]>CCCCCC.O1CCCC1>[CH:39]([C@@H:42]1[CH2:46][C@@H:45]([C@@H:47]([N:55]=[N+:56]=[N-:57])[CH2:48][C@@H:49]([CH:52]([CH3:53])[CH3:54])[CH:50]([OH:51])[C:21]2[CH:22]=[CH:23][C:18]([O:17][CH2:16][CH2:15][CH2:14][O:13][CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[C:19]([O:25][CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH:20]=2)[O:44][C:43]1=[O:58])([CH3:40])[CH3:41]

Komponenten

10

Edukt 7

HCID 78391,2-DibromoethaneHCID 25517Ammonium ChlorideHCID 82241Magnesium BromideHCID 5462224MagnesiumHCID 214586464-(3-Benzyloxypropyloxy)-3-(3-methoxypropyloxy)-bromobenzeneHCID 22865773(S)-2-[(S)-2-azido-2-((2S,4S)-4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-3-methyl-butyraldehydeHCID 178418339Butyllithium

Produkt 1

HCID 1317195743(S)-Isopropyl-5(S)-{1(S)-azido-3(S)-isopropyl-4(R,S)-hydroxy-4-(4-(3-benzyloxy-propyloxy)-3-(3-methoxypropyloxy)phenyl]-butyl}-tetrahydrofuran-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel3×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-75 °C

Versuchsvorschrift

1.3 ml of a 0.9M solution of butyllithium in hexane are slowly added dropwise to a solution, stirred at -75° C., of 500 mg of 4-(3-benzyloxypropyloxy)-3-(3-methoxypropyloxy)-bromobenzene in 2 ml of tetrahydrofuran. The reaction mixture is stirred for 20 minutes at -75° C., and then a suspension of magnesium bromide, freshly prepared from 44.5 mg of magnesium powder and 0.158 ml of 1,2-dibromoethane in 3 ml of tetrahydrofuran at room temperature, is added dropwise. The reaction mixture is stirred for a further 30 minutes at -75° C., and then a solution of 172 mg of 3(S)-isopropyl-5(S)-[1(S)-azido-3(S)-isopropyl-4-oxo-butyl]-tetrahydrofuran-2-one in 2 ml of tetrahydrofuran is added dropwise. The mixture is again stirred for 30 minutes at -75° C., and then 1.2 ml of saturated ammonium chloride solution are added dropwise at the same temperature. The reaction mixture is brought to room temperature and is then extracted three times with ethyl acetate. The organic phases are washed with water (2×) and saturated sodium chloride solution (1×), dried over magnesium sulfate, combined and concentrated by evaporation, and the residue is purified by means of FC (2×30 g of silica gel, hexane/ethyl acetate=6:2), yielding the title compound: Rt (hexane/ethyl acetate=2:1)=0.23; HPLC Rt =20.27 and 21.07 minutes (diastereoisomeric mixture); FAB-MS M+ =611.

Aufarbeitung

  1. additionis added dropwise
  2. stirringThe reaction mixture is stirred for a further 30 minutes at -75° C.
  3. stirringThe mixture is again stirred for 30 minutes at -75° C.
  4. customis brought to room temperature
  5. extractionis then extracted three times with ethyl acetate
  6. washThe organic phases are washed with water (2×) and saturated sodium chloride solution (1×)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated by evaporation
  9. customthe residue is purified by means of FC (2×30 g of silica gel, hexane/ethyl acetate=6:2)

Quellen und Nachweise

ORD-Eintrag
ord-27460c8b3d3c4fa5a6b8f6ba31e8931d
Quelldatensatz
uspto-grants-1998_01
Patentnummer
US05705658

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