4-Methylmorpholine → 3-Acetylthiomethyl-7-[{2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetyl}amino]-ceph-3-eme-4-carboxylic acid

HRID 1395332Notes

Reaction equation

HRID 1395332 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.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:48][CH:49]1[C:64](=[O:65])[N:51]2[C:52]([C:61]([OH:63])=[O:62])=[C:53]([CH2:56][S:57][C:58](=[O:60])[CH3:59])[CH2:54][S:55][C@H:50]12>C(N(CC)CC)C.C(Cl)Cl.O1CCCC1>[C:58]([S:57][CH2:56][C:53]1[CH2:54][S:55][C@@H:50]2[CH:49]([NH:48][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:64](=[O:65])[N:51]2[C:52]=1[C:61]([OH:63])=[O:62])(=[O:60])[CH3:59]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 886008887-Amino-3-acetylthiomethyl-ceph-3-eme-4-carboxylic acid

Product 1

HCID 1317117553-Acetylthiomethyl-7-[{2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetyl}amino]-ceph-3-eme-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

A mixture of 2.22 g of the anti isomer of 2-(2-tritylamino-4-thiazolyl)-2-methoxyimino-acetic acid, 20 ml of dry tetrahyrofuran, 15 ml of methylene chloride and 0.55 ml of N-methyl-morpholine under argon was cooled to -20° C. and 0.65 ml of isobutyl chloroformate was added thereto. The mixture was stirred and was cooled to -35° C. and then a solution of 1.44 g of 7-amino-3-acetylthiomethyl-ceph-3-eme-4-carboxylic acid, 25 ml of methylene chloride and 1.4 ml of anhydrous triethylamine was added thereto. The mixture spontaneously heated up and the solvents were removed. The residue was taken up in methylene chloride and 7 ml of N hydrochloric acid and the mixture was vacuum filtered. The filtrate was decanted and the aqueous phase was extracted with methylene chloride. The organic phase was washed with water, dried and vacuum filtered. The filtrate was evaporated to dryness to obtain 4.58 g of raw anti isomer of 3-acetylthiomethyl-7-[{2 -(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetyl}amino]-ceph-3-eme-4-carboxylic acid.

Workup

  1. temperaturewas cooled to -35° C.
  2. temperatureThe mixture spontaneously heated up
  3. customthe solvents were removed
  4. filtrationfiltered
  5. customThe filtrate was decanted
  6. extractionthe aqueous phase was extracted with methylene chloride
  7. washThe organic phase was washed with water
  8. customdried
  9. filtrationvacuum filtered
  10. customThe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-38c8b711ef554e3396e1051783d34bbe
Source dataset
uspto-grants-1980_05
Patent number
US04202893

Reaction notes

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