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 376573Notes

Reaction equation

HRID 376573 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 (740mg, 5.55mmol) was added to anisole (32ml) and dry dichloromethane (15ml) 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 (10ml). After 10 min., the solution was treated with trisodium citrate (0.5M, 54ml) and then vigorously stirred for 10 min. at room temperature. The aqueous phase was separated, washed with dichloromethane (x2) 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 (560mg, 64%); vmax (KBr) 3399, 1762, 1669, 1603, 1529, 1038cm-1 ; δH (d6 -DMSO, 250MHz) 1.50-1.91 (4H, m), 3.25 and 3.38 (2H, ABq, J 16.8Hz), 3.60-3.82 (2H, m), 3.84 (3H, s), 4.96 (1H, d, J 4.7Hz), 5.20 (1H, dd, J 8.6, 6.0Hz), 5.48 (1H, dd, J 8.1, 4.7Hz), 6.76 (1H, s), 7.23 (2H, br. s, exch.), 9.50 (1H, d, J 8.1Hz, 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 (x2)
  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-5f2a9960f01146c6955f95ae1acac6d8
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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