Tetrahydrofuran → sodium (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1649769Notes

Reaction equation

HRID 1649769 reaction equation
[NH2:1][C@@H:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH2:9][OH:10])[CH2:7][S:8][C@H:3]12.[OH-].[Na+:17].S1C2C=CC=CC=2N=C1S[O:28][C:29](=O)/[C:30](/[C:52]1[N:53]=[C:54]([NH:57][C:58]([C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[S:55][CH:56]=1)=[N:31]\[O:32][C:33]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.O1CCCC1>O.C(#N)C.O1CCOCC1>[C:58]([NH:57][C:54]1[S:55][CH:56]=[C:52](/[C:30](=[N:31]/[O:32][C:33]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)/[C:29]([NH:1][C@@H:2]2[C:14](=[O:15])[N:4]3[C:5]([C:11]([O-:13])=[O:12])=[C:6]([CH2:9][OH:10])[CH2:7][S:8][C@H:3]23)=[O:28])[N:53]=1)([C:71]1[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=1)([C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.[Na+:17]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 11031679(6R-trans)-7-Amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 884755391,3-benzothiazol-2-ylsulfanyl (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetate

Product 1

HCID 23676286sodium (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

In 20 ml of water is suspended 260 mg of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, and with ice-cooling and stirring, the suspension is adjusted to pH 7.0 with 1N-aqueous sodium hydroxide solution. After dissolution, 930 mg of 2-(2-tritylaminothiazol-4-yl)-(Z)-2-(trityloxyimino)acetic acid benzothiazol-2-ylthio ester, 20 ml of tetrahydrofuran, 20 ml of dioxane and 10 ml of acetonitrile are added and the mixture is stirred at room temperature for 38 hours. The reaction mixture is filtered and the filtrate is concentrated under reduced pressure. The residue is dissolved in 30 ml of tetrahydrofuran and the solution is subjected to silica gel (100 g) column chromatography. After the column is washed with acetonitrile (500 ml) and acetonitrile-water (19:1, 200 ml; 9:1, 200 ml), elution is carried out with 300 ml of acetonitrile-water (17:3). The eluate is concentrated under reduced pressure and the concentrate is freeze-dried to give 420 mg of sodium 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-(trityloxyimino)acetamido]-3-hydroxymethyl-3-cephem-4-carboxylate as light yellow powders.

Workup

  1. temperaturewith ice-cooling
  2. additionare added
  3. stirringthe mixture is stirred at room temperature for 38 hours
  4. filtrationThe reaction mixture is filtered
  5. concentrationthe filtrate is concentrated under reduced pressure
  6. dissolutionThe residue is dissolved in 30 ml of tetrahydrofuran
  7. washAfter the column is washed with acetonitrile (500 ml) and acetonitrile-water (19:1, 200 ml; 9:1, 200 ml), elution
  8. concentrationThe eluate is concentrated under reduced pressure
  9. customthe concentrate is freeze-dried

Sources & evidence

ORD record
ord-e3584286636d428ab14d7af07e0a1912
Source dataset
uspto-grants-1990_05
Patent number
US04921851

Reaction notes

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