Methyl triflate → O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(1-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioate

HRID 1707450Notes

Reaction equation

HRID 1707450 reaction equation
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]=[N:68][NH:69][CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:71](N(C(C)C)CC)(C)C.[CH3:80]OS(C(F)(F)F)(=O)=O>ClCCl.O1CCCC1>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:60])([CH3:61])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]([CH3:71])[N:68]=[N:69][CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:63])[C@@H:24]([NH:25][C:26](=[O:62])/[C:27](/[C:49]4[N:50]=[C:51]([NH:54][C:55]([O:57][C:58]([CH3:60])([CH3:61])[CH3:59])=[O:56])[S:52][CH:53]=4)=[N:28]\[O:29][C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@H:21]3[S:20][CH2:19][C:18]=2[CH2:64][S:65][C:66]2[N:67]=[N:68][N:69]([CH3:80])[CH:70]=2)=[S:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 9526Methyl triflateHCID 81531DiisopropylethylamineHCID 178452987HCID 178452987, compound

Product 2

HCID 141566154O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(3-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioateYield 30%HCID 141566156O-benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-[(1-methyltriazol-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbothioateYield 46%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (6.00 g: 5.87 mMol.) in a mixture of dichloromethane (60 ml) and tetrahydrofuran (30 ml) is added at -50° C. diisopropylethylamine (1.12 g: 6.43 mMol.). After stirring at -40°--50° C. for 3 minutes, trifluoromethanesulfonic acid methyl ester (0.73 ml: 6.45 mMol.) is added to the mixture. After stirring at the same temperature for 30 minutes, the reaction mixture is quenched with 10% hydrochloric acid (2.4 ml), diluted with water, and extracted with ethyl acetate. The extract is washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene: ethyl acetate=3:2) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(3-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester [1.84 g: Yield: 30%. NMR δ(CDCl3 -CD3OD) ppm: 1.52(s, 9H), 3.43, 3.55(ABq, J=17.3 Hz, 2H), 3.87, 3.94(ABq, J=13.7 Hz, 2H), 3.95(s, 3H), 5.12 (d, J=4.8 Hz, 1H), 5.99 (d, J=4.8 Hz, 1H), 6.96 (s, 1H), 7.06(s, 1H), 7.15-7.50(m, 25H), 7.73(s, 1H). IR ν(CHCl3) cm-1: 3398, 3300, 1784, 1714, 1683, 1540, 1490, 1443, 1366, 1277, 1220, 1153, 1114, 1077, 970, 910.], 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(1-methyl-1,2,3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (2.71 g: Yield: 46%), and 7β-[(Z)-2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-trityloxyiminoacetamido]-3-(2-methyl-1,2,3-triazol-4-yl)-thiomethylthio-3-cephem-4-carboxylic acid diphenylmethyl ester (0.51 g: Yield: 8%).

Workup

  1. stirringAfter stirring at the same temperature for 30 minutes
  2. customthe reaction mixture is quenched with 10% hydrochloric acid (2.4 ml)
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe extract is washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=3:2)

Sources & evidence

ORD record
ord-ee7c03e232dc4871a9c4adcb20725e55
Source dataset
uspto-grants-1994_10
Patent number
US05352792

Reaction notes

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