Hydrochloric Acid → 3-Acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 467254Notes

Reaction equation

HRID 467254 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][CH3:32])[C:27]([OH:29])=O)[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.[CH3:44][C:45]([O:47][CH2:48][C:49]1[CH2:58][S:57][C@@H:52]2[C@H:53]([NH2:56])[C:54](=[O:55])[N:51]2[C:50]=1[C:59]([OH:61])=[O:60])=[O:46].Cl>C(Cl)CCl.C(N(CC)CC)C.O.C(O)(=O)C.CN(C)C=O>[C:45]([O:47][CH2:48][C:49]1[CH2:58][S:57][C@@H:52]2[CH:53]([NH:56][C:27](=[O:29])[C:26]([C:24]3[N:25]=[C:21]([NH:20][C:1]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[S:22][CH:23]=3)=[N:30][O:31][CH3:32])[C:54](=[O:55])[N:51]2[C:50]=1[C:59]([OH:61])=[O:60])(=[O:46])[CH3:44]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 4413287-Aminocephalosporanic acidHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acid

Product 1

HCID 1317115023-Acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent2×

Procedure

576.5 g of the syn isomer of 2-(2-tritylamino-4-thiazolyl)-2-methoxyimino-acetic acid were added at 0° C. to a solution of 247.8 g of tosyl chloride in 780 m. of dimethylformamide and then 196 ml of triethylamine were added thereto. The mixture was held at 0° C. while adding thereto a solution of 272 g of 7-amino-cephalosporanic acid in 3 liters of ethylene chloride and 450.7 ml of triethylamine cooled to -70° to -75° C. and the mixture was held at -20° C. for 30 minutes. Then 270 ml of acetic acid followed by 540 ml of demineralized water were added thereto and the temperature rose to -15° to -20° C. 11 liters of demineralized water were added thereto and the pH was adjusted to 1 to 1.2 by addition of 0.1N hydrochloric acid. The decanted organic phase was washed 3 times with 2700 ml of demineralized water and was concentrated under reduced pressure in a bath at 8° to 30° C. to a volume of 1350 ml to obtain a solution of syn isomer of 3-acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyimino-acetamido]-ceph-3-eme-4-carboxylic acid.

Workup

  1. customwas held at 0° C.
  2. additionwhile adding
  3. additionwere added
  4. customrose to -15° to -20° C
  5. washThe decanted organic phase was washed 3 times with 2700 ml of demineralized water
  6. concentrationwas concentrated under reduced pressure in a bath at 8° to 30° C. to a volume of 1350 ml

Sources & evidence

ORD record
ord-2700d5f00d264b67ab2b920da6a9729a
Source dataset
uspto-grants-1992_10
Patent number
US05159070

Reaction notes

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