Trisodium citrate → sodium (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2R)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1421798Notes

Reaction equation

HRID 1421798 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 88258980(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2R)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 88280324sodium (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2R)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Aluminium chloride (740 mg, 5.55 mmol) was added to anisole (32 ml) and dry dichloromethane (15 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-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (1.06 g, 1.85 mmol) in dichloromethane (10 ml). After 1 min., the solution was treated with trisodium citrate (0.5M, 54 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 (560 mg, 64%); νmax (KBr) 3399, 1762, 1669, 1603, 1529, 1038 cm-1 ; δH (d6 -DMSO, 250 MHz) 1.50-1.91 (4H, m), 3.25 and 3.38 (2H, ABq, J 16.8 Hz), 3.60-3.82 (2H, m), 3.84 (3H, s), 4.96 (1H, d, J 4.7 Hz), 5.20 (1H, dd, J 8.6, 6.0 Hz), 5.48 (1H, dd, J 8.1, 4.7 Hz), 6.76 (1H, s), 7.23 (2H, br. s, exch.), 9.50 (1H, d, J 8.1 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (476), MNa+ (498)].

Workup

  1. waitAfter 1 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-27cddfd17d654eed920342aa48cb447e
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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