HCID 131713656, compound → HCID 178462780, compound

HRID 358170Notes

Reaction equation

HRID 358170 reaction equation
[Na+].C(O[CH2:6][C:7]1[CH2:8][S:9][C@@H:10]2[C@H:17]([NH:18][C:19](=[O:50])[C@@H:20]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([O:43][CH2:44][C@@H:45]([NH2:49])[C:46]([OH:48])=[O:47])=[O:42])=[CH:36][CH:35]=3)[NH:21][C:22]([N:24]3[CH2:29][CH2:28][N:27]([CH2:30][CH3:31])[C:26](=[O:32])[C:25]3=[O:33])=[O:23])[C:16](=[O:51])[N:11]2[C:12]=1[C:13]([O-:15])=[O:14])(=O)C.CN(C)CC[N:56]1[C:60]([SH:61])=[N:59][N:58]=[N:57]1>>[CH3:12][N:11]([CH3:16])[CH2:10][CH2:17][CH:6]([S:61][C:60]1[NH:59][N:58]=[N:57][N:56]=1)[C:7]1[CH2:8][S:9][C@@H:10]2[C@H:17]([NH:18][C:19](=[O:50])[C@@H:20]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([O:43][CH2:44][C@@H:45]([NH2:49])[C:46]([OH:48])=[O:47])=[O:42])=[CH:36][CH:35]=3)[NH:21][C:22]([N:24]3[CH2:29][CH2:28][N:27]([CH2:30][CH3:31])[C:26](=[O:32])[C:25]3=[O:33])=[O:23])[C:16](=[O:51])[N:11]2[C:12]=1[C:13]([OH:15])=[O:14]

Participants

3

Reactant 2

HCID 131713656HCID 131713656, compoundHCID 178483731HCID 178483731, compound

Product 1

HCID 178462780HCID 178462780, compound

Procedure

2.3 g of 3-acetoxymethyl-7β-{(2R)-2-[4-((2R)-2-amino-2-carboxyethoxycarbonylamino)-phenyl]-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)-acetamido}-3-cephem-4-carboxylic acid sodium salt and 1.16 g of 1-(2-dimethylaminoethyl)-5-mercapto-1H-tetrazole are dissolved in 12 ml of twice-distilled and degassed water. The solution is then adjusted to a pH of 6.2 with 1N aqueous NaOH and then stirred at 65° for 4 hours under a nitrogen atmosphere. It is then cooled, adjusted to a pH of 5 with 1N HCl and introduced into 600 ml of ethanol. The resulting precipitate is filtered with suction, washed with alcohol and ether and dried. The crude product is then separated over a column of 100 g of silylated silica gel (Opty-Up C 12; ANTEC AG, CH-4431 Bennwil) and 40 ml fractions are taken. Fractions 1-13 are eluted with H2O/acetonitrile (97:3), fractions 14-20 with H2O/acetonitrile (93:7), fractions 21-28 with H2O/acetonitrile (9:1) and the later fractions with H2O/acetonitrile (4:1). By concentrating by evaporation and reprecipitating from H2O/ethanol fractions 33-35, 3-[1-(2-dimethylaminoethyl)-1H-tetrazol-5-ylthiomethyl]-7β-{(2R)-2-[4-((2R)-2-amino-2-carboxyethoxycarbonylamino)-phenyl]-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)-acetamido}-3-cephem-4-carboxylic acid is obtained. Decomposition from 165°. [α]D20 =+34°±1° (0.67% in H2O). IR: 3400 (shoulder), 3280 (wide), 1770, 1720, 1680, 1612, 1515 cm-1 (Nujol).

Workup

  1. distillationof twice-distilled
  2. customdegassed water
  3. temperatureIt is then cooled
  4. additionintroduced into 600 ml of ethanol
  5. filtrationThe resulting precipitate is filtered with suction
  6. washwashed with alcohol and ether
  7. customdried
  8. customThe crude product is then separated over a column of 100 g of silylated silica gel (Opty-Up C 12; ANTEC AG, CH-4431 Bennwil) and 40 ml fractions
  9. washFractions 1-13 are eluted with H2O/acetonitrile (97:3), fractions 14-20 with H2O/acetonitrile (93:7), fractions 21-28 with H2O/acetonitrile (9:1)
  10. concentrationBy concentrating by evaporation
  11. customreprecipitating from H2O/ethanol fractions 33-35

Sources & evidence

ORD record
ord-030c2392c4b34caf9dc414e443d8ba1c
Source dataset
uspto-grants-1984_08
Patent number
US04464366

Reaction notes

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