ethyl (Z)-2-bromomethylbut-2-enoate → [(Z)-2-ethoxycarbonylbut-2-enyl] (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

HRID 376618Notes

Reaction equation

HRID 376618 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:28]/[O:29][CH3:30])/[C:8]([NH:10][C@@H:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([O-:25])=[O:24])=[C:15]([C@@H:18]4[CH2:22][CH2:21][CH2:20][O:19]4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+].Br[CH2:33]/[C:34](=[CH:40]\[CH3:41])/[C:35]([O:37][CH2:38][CH3:39])=[O:36]>CN1CCCC1=O.C(OCC)(=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:28]/[O:29][CH3:30])/[C:8]([NH:10][C@@H:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([O:25][CH2:33]/[C:34](/[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:40]/[CH3:41])=[O:24])=[C:15]([C@@H:18]4[CH2:22][CH2:21][CH2:20][O:19]4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

5

Reactant 2

HCID 10420543ethyl (Z)-2-bromomethylbut-2-enoateHCID 23690298Cefovecin sodium

Product 1

HCID 141582266[(Z)-2-ethoxycarbonylbut-2-enyl] (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

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

Sodium (6R,7R)-7-[2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate, (0.35g) in 1-methyl-2-pyrrolidinone (4ml) was treated with a solution of ethyl (Z)-2-bromomethylbut-2-enoate, (0.16g) in 1-methyl-2-pyrrolidinone (1ml) and stirred at ambient temperature overnight. The solution was diluted with ethyl acetate and washed with water (3x), brine and then dried. After removal of solvent in vacuo, the residue was purified by flash chromatography on silica gel, eluting with 70, 90% ethyl acetate-hexane and then ethyl acetate. The title compound was obtained as a pale yellow foam (0.368g, 86%); vmax (CH2Cl2) 3480, 3389, 3320, 1781, 1726, 1682, 1606 and 1532cm-1 ; δH (CDCl3) 1.30 (4H, t, J 7.1Hz, overlapping M), 1.66 (1H, m), 1.97 (3H, d, J 7.3Hz), 2.35 (1H, m), 3.33 and 3.64 (2H, ABq, J 18.7Hz), 3.88 (2H, m), 4.08 (3H, s), 4.22 (2H, q, J 7.1Hz), 4.93 (1H, m), 5.05 (3H, m), 5.80 (2H, br s, exch.), 5.99 (1H, dd, J 4.8, 9.0Hz, collapses to d, J 4.8Hz on exch.), 6.83 (1H, s), 7.21 (1H, q, J 7.3Hz) and 7.73 (1H, d, J 9.0Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (580)].

Workup

  1. washwashed with water (3x), brine
  2. customdried
  3. customAfter removal of solvent in vacuo
  4. customthe residue was purified by flash chromatography on silica gel
  5. washeluting with 70, 90% ethyl acetate-hexane

Sources & evidence

ORD record
ord-b32efb96407c4dfa9703e3035e88d4af
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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