Sodium hydride → benzhydryl (7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanyl)-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 2214769Notes

Reaction equation

HRID 2214769 reaction equation
[S:1]1[CH:5]=[N:4][N:3]=[C:2]1[SH:6].[H-].[Na+].[C:9]1([CH:15]([O:22][C:23]([C:25]2[N:26]3[CH:29]([CH2:30][CH2:31][C:32]=2Cl)[C@@H:28]([NH:34][C:35](=[O:65])/[C:36](/[C:58]2[N:59]=[C:60]([NH2:64])[S:61][C:62]=2[Cl:63])=[N:37]\[O:38][C:39]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:27]3=[O:66])=[O:24])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(#N)C>[C:9]1([CH:15]([O:22][C:23]([C:25]2[N:26]3[CH:29]([CH2:30][CH2:31][C:32]=2[S:6][C:2]2[S:1][CH:5]=[N:4][N:3]=2)[C@@H:28]([NH:34][C:35](=[O:65])/[C:36](/[C:58]2[N:59]=[C:60]([NH2:64])[S:61][C:62]=2[Cl:63])=[N:37]\[O:38][C:39]([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:27]3=[O:66])=[O:24])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 140482359benzhydryl (7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 178527973HCID 178527973, compound

Product 1

HCID 140482356benzhydryl (7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanyl)-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 1,3,4-thiadiazole-2-thiol (0.5 g, 0.004 mol) in acetonitile (40 mL) was added sodium hydride (0.2 g, 0.0043 mol) and the mixture was stirred for 1 hour at room temperature. To the resulting suspension was added (7R)-7-[(Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(triphenylmethoxyimino]-acetamido]-3-chloro-8-oxo-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate diphenylmethyl ester (2.6 g, 0.003 mol), and the mixture was stirred for 48 hours. The solvent was evaporated and the residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was dried over anhydrous MgSO4, filtered and evaporated. The resulting solid was treated with diethyl ether (50 mL), and the solid that formed was filtered and dried to give 2.1 g of crude product. The crude product was purified by chromatography on silica gel, eluting with a gradient from ethyl acetate:hexane 1:2 to neat ethyl acetate. The title product was obtained (1.1 g.)

Workup

  1. stirringthe mixture was stirred for 48 hours
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between water (50 mL) and ethyl acetate (50 mL)
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. additionThe resulting solid was treated with diethyl ether (50 mL)
  8. customthe solid that formed
  9. filtrationwas filtered
  10. customdried
  11. customto give 2.1 g of crude product
  12. customThe crude product was purified by chromatography on silica gel
  13. washeluting with a gradient from ethyl acetate:hexane 1:2 to neat ethyl acetate

Sources & evidence

ORD record
ord-bd394d326526450c841114b54f605ac3
Source dataset
uspto-grants-2006_09
Patent number
US07109190B2

Reaction notes

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