Diphenyl chlorophosphate → HCID 86744491, 화합물

HRID 703602노트

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HRID 703602 반응식
[N+](=[C:3]([C:10](=O)[C@@H:11]([C@@H:13]1[C@@H:16]([C@H:17]([OH:19])[CH3:18])[C:15](=[O:20])[NH:14]1)[CH3:12])[C:4]([O:6][CH2:7][CH:8]=[CH2:9])=[O:5])=[N-].P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.C(N(C(C)C)CC)(C)C.C([S:51][C@@H:52]1[CH2:56][N:55]([C:57]([O:59][CH2:60][CH:61]=[CH2:62])=[O:58])[C@H:54]([CH2:63][O:64][CH2:65][CH:66]([F:68])[CH3:67])[CH2:53]1)(=O)C.C[O-].[Na+]>C(OCC)(=O)C.C(#N)C.C([O-])(=O)CCCCCCC.[Rh+2].C([O-])(=O)CCCCCCC.O.CN(C)C(=O)C>[CH2:60]([O:59][C:57]([N:55]1[CH2:56][C@@H:52]([S:51][C:10]2[C@H:11]([CH3:12])[C@H:13]3[N:14]([C:15](=[O:20])[C@@H:16]3[C@H:17]([OH:19])[CH3:18])[C:3]=2[C:4]([O:6][CH2:7][CH:8]=[CH2:9])=[O:5])[CH2:53][C@H:54]1[CH2:63][O:64][CH2:65][CH:66]([F:68])[CH3:67])=[O:58])[CH:61]=[CH2:62]

참가 물질

11

반응물 5

HCID 75654Diphenyl chlorophosphateHCID 81531DiisopropylethylamineHCID 10942334Sodium MethoxideHCID 18642552HCID 18642552, 화합물HCID 54331596(3S,4R)-3-[(R)-1-hydroxyethyl]-4-[(R)-1-methyl-3-diazo-3-allyloxycarbonyl-2-oxopropyl]-2-azetidinone

생성물 1

HCID 86744491HCID 86744491, 화합물수율 27.1%

시약·촉매·용매 5

HCID 10178397Rhodium(II) octanoate촉매HCID 962Water용매HCID 6342Acetonitrile용매2회HCID 8857Ethyl Acetate용매2회HCID 31374Dimethylacetamide용매

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온도
0 °C

실험 절차

To a solution of allyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (621 mg) in ethyl acetate (10 ml) was added rhodium(II) octanoate (10 mg) under nitrogen atmosphere, which was heated under reflux for 30 minutes. The solvent was evaporated and the remaining ethyl acetate was removed as the acetonitrile (10 ml) azeotrope to give a residue, which was dissolved in acetonitrile (10 ml) and cooled to 0° C. under nitrogen atmosphere. To the solution were added diphenyl chlorophosphate (480 μl), N,N-diisopropyl-N-ethylamine (421 μl) and N,N-dimethylacetamide (5 ml), and the solution was stirred for 10 hours at 0° C. To the solution was added at 0° C. a reaction mixture of (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidine (790 mg) and 28% sodium methoxide (485 μl) in acetonitrile (5 ml) which reaction had been carried out at -20° C. for 15 minutes. The reaction mixture was allowed to warm at ambient temperature and stirred for 5 hours, which was poured into a mixture of ethyl acetate (50 ml) and water (20 ml). The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo to give a residue, which was chromatographed on silica gel (100 ml) eluting with a mixture of hexane and ethyl acetate (1:1-1:2 V/V) to give allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (300 mg).

후처리

  1. temperaturewhich was heated
  2. temperatureunder reflux for 30 minutes
  3. customThe solvent was evaporated
  4. customthe remaining ethyl acetate was removed as the acetonitrile (10 ml)
  5. customto give a residue, which
  6. additionTo the solution was added at 0° C.
  7. waithad been carried out at -20° C. for 15 minutes
  8. temperatureto warm at ambient temperature
  9. stirringstirred for 5 hours
  10. customThe organic layer was separated
  11. washwashed with brine
  12. dry with materialdried over magnesium sulfate
  13. customevaporated in vacuo
  14. customto give a residue, which
  15. customwas chromatographed on silica gel (100 ml)
  16. washeluting with a mixture of hexane and ethyl acetate (1:1-1:2 V/V)

출처 및 근거

ORD 기록
ord-5e1a8f35c3644ae6be0cfd319b0fd3f0
출처 데이터셋
uspto-grants-1991_01
특허 번호
US04983596

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