Sodium borohydride → benzhydryl (7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-[[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylsulfanylmethyl]-3-pyridinyl]sulfanyl]-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 2214772Notes

Reaction equation

HRID 2214772 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[C:17]([S:18]SC2C(C(CCNC(OC(C)(C)C)=O)S)=NC=CC=2)=[CH:16][CH:15]=[CH:14][N:13]=1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].[C:41]1([CH:47]([O:54][C:55]([C:57]2[N:58]3[CH:61]([CH2:62][CH2:63][C:64]=2Cl)[C@@H:60]([NH:66][C:67](=[O:97])/[C:68](/[C:90]2[N:91]=[C:92]([NH2:96])[S:93][C:94]=2[Cl:95])=[N:69]\[O:70][C:71]([C:84]2[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=2)([C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[C:59]3=[O:98])=[O:56])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(#N)C>[C:41]1([CH:47]([O:54][C:55]([C:57]2[N:58]3[CH:61]([CH2:62][CH2:63][C:64]=2[S:18][C:17]2[C:12]([CH2:11][S:10][CH2:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:38])=[N:13][CH:14]=[CH:15][CH:16]=2)[C@@H:60]([NH:66][C:67](=[O:97])/[C:68](/[C:90]2[N:91]=[C:92]([NH2:96])[S:93][C:94]=2[Cl:95])=[N:69]\[O:70][C:71]([C:84]2[CH:85]=[CH:86][CH:87]=[CH:88][CH:89]=2)([C:78]2[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=2)[C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[C:59]3=[O:98])=[O:56])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 86595759(2-{3-[2-(2-Tert-butoxycarbonylaminoethyl-sulfanylmethyl)-pyridin-3-yldisulfanyl]-pyridin-2-ylmethylsulfanyl}ethyl)carbamic acid tert-butyl esterHCID 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-carboxylate

Product 1

HCID 140482357benzhydryl (7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-[[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylsulfanylmethyl]-3-pyridinyl]sulfanyl]-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 47.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (2-{3-[2-(2-tert-butoxycarbonylaminoethyl-sulfanylmethyl)-pyridin-3-yldisulfanyl]-pyridin-2-ylmethylsulfanyl}ethyl)carbamic acid tert-butyl ester (1.3 g, 0.0022 mol) in acetonitrile (120 mL) was added sodium borohydride (0.12 g, 0.003 mol), and the mixture was stirred at room temp. for 18 hours. (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 (3.6 g, 0.0043 mol) was added in portions and the mixture was heated at reflux for 6 hours. The solvent was evaporated and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was separated, dried over anhydrous MgSO4 and concentrated. The residue was treated with diethyl ether (50 mL), and the solid that formed was filtered and dried to give 3.6 g of crude product. The crude product was purified by column chromatography on silica gel (100 g), eluting with hexane: ethyl acetate 1:1, to give the title compound (1.15 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 6 hours
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated
  8. additionThe residue was treated with diethyl ether (50 mL)
  9. customthe solid that formed
  10. filtrationwas filtered
  11. customdried
  12. customto give 3.6 g of crude product
  13. customThe crude product was purified by column chromatography on silica gel (100 g)
  14. washeluting with hexane: ethyl acetate 1:1

Sources & evidence

ORD record
ord-55de68ca3c3041399ff89b53d5a99e79
Source dataset
uspto-grants-2006_09
Patent number
US07109190B2

Reaction notes

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