Trisodium citrate → Cefovecin sodium

HRID 1421796Notes

Reaction equation

HRID 1421796 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].C1(OC)C=CC=CC=1.[NH2:13][C:14]1[S:15][CH:16]=[C:17](/[C:19](=[N:49]/[O:50][CH3:51])/[C:20]([NH:22][C@@H:23]2[C:47](=[O:48])[N:25]3[C:26]([C:35]([O:37]CC4C=CC(OC)=CC=4)=[O:36])=[C:27]([C@@H:30]4[CH2:34][CH2:33][CH2:32][O:31]4)[CH2:28][S:29][C@H:24]23)=[O:21])[N:18]=1.C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O.[Na+:65].[Na+].[Na+]>ClCCl>[NH2:13][C:14]1[S:15][CH:16]=[C:17](/[C:19](=[N:49]/[O:50][CH3:51])/[C:20]([NH:22][C@@H:23]2[C:47](=[O:48])[N:25]3[C:26]([C:35]([O-:37])=[O:36])=[C:27]([C@@H:30]4[CH2:34][CH2:33][CH2:32][O:31]4)[CH2:28][S:29][C@H:24]23)=[O:21])[N:18]=1.[Na+:65]

Participants

6

Reactant 4

HCID 6224Trisodium citrateHCID 7519AnisoleHCID 6451240Aluminum(III) ChlorideHCID 141582268(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2S)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 23690298Cefovecin sodiumYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Aluminium chloride (162 mg, 1.21 mmol) was added to anisole (7 ml) and dry dichloromethane (3.5 ml) at -20° C. and stirred for 15 min. The temperature of the cooling bath was then lowered to -40° C. before addition of a solution of 4-methoxybenzyl (6R,7R)-7-[2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (235 mg, 0.41 mmol) in dichloromethane (5 ml). After 10 min., the solution was treated with trisodium citrate (0.5M, 12 ml) and then vigorously stirred for 10 min at room temperature. The aqueous phase was separated, washed with dichloromethane (×2) and concentrated in vacuo. The residue was chromatographed on HP20SS eluting with water, then 1% THF in water. Fractions containing the product, (h.p.l.c. analysis), were combined and freeze-dried to give the title compound (126 mg, 65%); νmax (KBr) 3401, 1761, 1669, 1603, 1533, 1040 cm-1 ; δH (d6 -DMSO, 250 MHz) 1.43-1.59 (1H, m), 1.71-1.88 (2H, m), 2.0-2.12 (1H, m), 3.18 and 3.37 (2H, ABq, J 17.4 Hz), 3.58 (1H, m), 3.78 (1H, m), 3.81 (3H, s), 4.87 (1H, dd, J 8.7, 6.7 Hz), 4.97 (1H, d, J 4.7 Hz), 5.50 (1H, dd, J 8.1, 4.7 Hz), 6.74 (1H, s), 7.21 (2H, br. s, exch.), 9.48 (1H, d, J 8.1 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (476), MNa+ (498)].

Workup

  1. waitAfter 10 min.
  2. stirringvigorously stirred for 10 min at room temperature
  3. customThe aqueous phase was separated
  4. washwashed with dichloromethane (×2)
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on HP20SS
  7. washeluting with water
  8. additionFractions containing the product, (h.p.l.c. analysis),
  9. customfreeze-dried

Sources & evidence

ORD record
ord-f88b0343ac7c4881bb4ec7c5e41a829f
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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