Hydrochloric Acid → HCID 178521500, compound

HRID 249609Notes

Reaction equation

HRID 249609 reaction equation
C1(C([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:26])[C@@H:24]([NH2:25])[C@H:21]3[S:20][CH2:19][C:18]=2[S:27][CH:28]([C:35](C2C=CC=CC=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[S:29][C:30]2[N:31]=[N:32][NH:33][CH:34]=2)=[O:16])C2C=CC=CC=2)C=CC=CC=1.[C:54]([NH:73][C:74]1[S:75][CH:76]=[C:77]([C:79](=[N:83][O:84][CH2:85][C:86]([O:88][CH:89]([C:96]2[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=2)[C:90]2[CH:95]=[CH:94][CH:93]=[CH:92][CH:91]=2)=[O:87])C(O)=O)[N:78]=1)([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.CN1CC[O:106][CH2:105]C1.P(Cl)(Cl)(O[C:112]1[CH:117]=[CH:116][CH:115]=[CH:114][CH:113]=1)=O.Cl>ClC.O>[C:54]([NH:73][C:74]1[S:75][CH:76]=[C:77](/[C:79](=[N:83]/[O:84][CH2:85][C:86]([O:88][CH:89]([C:90]2[CH:95]=[CH:94][CH:93]=[CH:92][CH:91]=2)[C:96]2[CH:101]=[CH:100][CH:99]=[CH:98][CH:97]=2)=[O:87])/[C:105]([NH:25][C@@H:24]2[C:23](=[O:26])[N:22]3[C:17]([C:15]([OH:14])=[O:16])=[C:18]([S:27][CH:28]([C:35]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)([C:112]4[CH:117]=[CH:116][CH:115]=[CH:114][CH:113]=4)[C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[S:29][C:30]4[N:31]=[N:32][NH:33][CH:34]=4)[CH2:19][S:20][C@H:21]23)=[O:106])[N:78]=1)([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 13038Phosphorodichloridic acid, phenyl esterHCID 54272188HCID 54272188, compoundHCID 178511753HCID 178511753, compound

Product 1

HCID 178521500HCID 178521500, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6327Methyl ChlorideSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 7β-amino-3-(trityl-1,2,3-triazol-4-ylthiomethyl- thio) -3-cephem-4-carboxylic acid diphenylmethyl ester (800 mg : 1.06 mMol.) and (Z) 2-(2-tritylaminothiazol-4-yl) -2-(diphenylmethoxycarbonylmethoxyimino)acetic acid (728 mg : 1.11 mMol.) in chloromethane (8 ml) cooling at -30° C., are added N-methylmorpholine (0.27 ml : 2.46 mMol.), phenyl dichlorophosphate (0.19 ml : 1.27 mMol.), and the mixture is stirred at -30° C. for 30 minutes. The reaction mixture is mixed with 10% hydrochloric acid (1 ml), diluted with water, and extracted with ethyl acetate. The extract is washed with brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene : ethyl acetate=10:1) to give 7β-[(Z)-2-(2-tritylaminothiazol-4-yl)-2-(diphenylmethoxycarbonylmethoxyimino)acetamido]-3- (trityl-1,2,3-triazol-4-ylthiomethylthio) -3-cephem-4-carboxylic acid (dipbenylmethyl ester (1.07 g) as yellow foam. Yield : 73%. NMR δ (CDCl3) ppm: 3.32, 3.62(ABq, J=17.1Hz, 2H), 4.07, 4.12(ABq, J=13.2 Hz, 2H), 4.90(d, J=5.0Hz, 1H), 4.93, 5.03(ABq, J=17.0Hz, 2H), 5.80 (dd, J=9.1Hz, J=5.0Hz, 1H), 6.81(s, 1H), 6.87(s, 1H), 6.93(s, 1H), 7.0-7.4(m, 51H), 7.45(s, 1H), 8.11(d, J=9.1Hz, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract is washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel chromatography (toluene : ethyl acetate=10:1)

Sources & evidence

ORD record
ord-ce8a930a64c94ccb8a958293ab8c83d1
Source dataset
uspto-grants-1993_05
Patent number
US05214037

Reaction notes

Loading…