Acetonitrile → HCID 86592514, compound

HRID 1374399Notes

Reaction equation

HRID 1374399 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Si]([O:18][CH2:19][C@@H:20]1[C:24]([C:25]2[N:26]=[C:27]([SH:30])[S:28][CH:29]=2)=[CH:23][CH2:22][N:21]1[C:31]([O:33][CH2:34][CH:35]=[CH2:36])=[O:32])(C(C)(C)C)(C)C.O(P(OC1C=CC=CC=1)O[C:46]1[C@H:52]([CH3:53])[C@H:51]2[N:48]([C:49](=[O:61])[C@@H:50]2[C@H:54]([O:56][Si](C)(C)C)[CH3:55])[C:47]=1[C:62]([O:64][CH2:65][CH:66]=[CH2:67])=[O:63])C1C=CC=CC=1.C(#N)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(O)(=O)C>[CH2:34]([O:33][C:31]([N:21]1[CH2:22][CH:23]=[C:24]([C:25]2[N:26]=[C:27]([S:30][C:46]3[C@H:52]([CH3:53])[C@H:51]4[N:48]([C:49](=[O:61])[C@@H:50]4[C@H:54]([OH:56])[CH3:55])[C:47]=3[C:62]([O:64][CH2:65][CH:66]=[CH2:67])=[O:63])[S:28][CH:29]=2)[C@H:20]1[CH2:19][OH:18])=[O:32])[CH:35]=[CH2:36]

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 86592502HCID 86592502, compoundHCID 178459667HCID 178459667, compound

Product 1

HCID 86592514HCID 86592514, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of lithium hexamethyldisilazide in THF (1M, 0.16 ml, 0.16 mmol) was added at 0–5° C. to a solution of allyl (2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(2-mercapto-1,3-thiazol-4-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate (67 mg, 0.16 mmol) in THF (0.3 ml) and the mixture was stirred for 20 minutes. To the reaction solution was added at 0° C. a solution of allyl (4R,5R,6S)-3-[(diphenoxyphosphino)oxy]-4-methyl-7-oxo-6-{(1R)-1-[(trimethylsilyl)oxy]ethyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in acetonitrile (30%, 0.62 g, 0.32 mmol) and the solution was allowed to stand in a refrigerator for 12 hours. To the reaction solution was added ice water and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/5→1/3) to give a mixture of a coupling compound and POCA (Starting material). To the mixture in THF (2.4 ml) were added at 0–5° C. acetic acid (92 μl) and tetrabutylammonium fluoride in THF (1M, 0.96 ml, 0.96 mmol). After reaction for 20 hours, to the reaction mixture was added ice water and the solution was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/3→10% methanol/chloroform) to give allyl (4R,5S,6S)-3-({4-[(2S)-1-[(allyloxy)carbonyl]-2-(hydroxymethyl)-2,5-dihydro-1H-pyrrol-3-yl]-1,3-thiazol-2-yl}sulfanyl)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (83 mg, 95%).

Workup

  1. waitto stand in a refrigerator for 12 hours
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customAfter removal of the solvent in vacuo
  6. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/5→1/3)
  7. customto give
  8. additiona mixture of a coupling compound and POCA (Starting material)
  9. customAfter reaction for 20 hours
  10. extractionthe solution was extracted with ethyl acetate
  11. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. customAfter removal of the solvent in vacuo
  14. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate: 1/3→10% methanol/chloroform)

Sources & evidence

ORD record
ord-18b404047cca41dcad4a2c0b88507bb7
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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