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 744815노트

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HRID 744815 반응식
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]

참가 물질

10

반응물 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

생성물 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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 8058Hexane용매

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온도
-75 °C

실험 절차

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 (2x) and saturated sodium chloride solution (1x), 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: Rf (hexane/ethyl acetate=2:1)=0.23; HPLC Rt =20.27 and 21.07 minutes (diastereoisomeric mixture); FAB-MS M+ =611.

후처리

  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 (2x) and saturated sodium chloride solution (1x)
  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)

출처 및 근거

ORD 기록
ord-553725c85bb243b0ac50534a8b8e9ef4
출처 데이터셋
uspto-grants-1996_09
특허 번호
US05559111

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