4-Methylmorpholine → HCID 178525024, compound

HRID 249606Notes

Reaction equation

HRID 249606 reaction equation
[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:26])[C@@H:24](N)[C@H:21]3[S:20][CH2:19][C:18]=2[S:27][CH:28]([C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=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])[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(OC(NC1SC=C(CC(O)=O)N=1)=O)(C)(C)C.CN1CCOCC1.P(Cl)(Cl)(OC1C=CC=CC=1)=O>ClCCl>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:22]3[C:23](=[O:26])[CH2:24][C@H:21]3[S:20][CH2:19][C:18]=2[S:27][CH:28]([C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[S:29][C:30]2[N:31]=[N:32][NH:33][CH:34]=2)=[O: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

6

Reactant 4

HCID 79724-MethylmorpholineHCID 13038Phosphorodichloridic acid, phenyl esterHCID 154800062-(2-((tert-Butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 178511753HCID 178511753, compound

Product 1

HCID 178525024HCID 178525024, compoundYield 103.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 2-(2-t-butoxycarbonylaminothiazol-4-yl) acetic acid (287 mg : 1.11 mMol.) in dichloromethane (8 ml) cooling at -30° C. are added N- methylmorpholine (0.27 ml: 2.46 mMol.) and phenyl dichlorophosphate (0.19 ml : 1.27 mMol.), and the mixture is stirred at -30° C. for 40 minutes. The reaction mixture is quenched 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=3:1) to give 7β-2-(2-t-butoxycarbonylaminothiazol- 4-yl) acetamido]-3-(trityl-1,2,3-triazol-4-ylthiomethylthio) -3-cephem-4- carboxylic acid diphenylmethyl ester (812 mg) as pale yellow foam Yield : 77%.

Workup

  1. customThe reaction mixture is quenched with 10% hydrochloric acid (1 ml)
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. washThe extract is washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography (toluene : ethyl acetate=3:1)

Sources & evidence

ORD record
ord-9549b1e671324dd3b89ff9c3e48c8014
Source dataset
uspto-grants-1993_05
Patent number
US05214037

Reaction notes

Loading…