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 1421838Notes

Reaction equation

HRID 1421838 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, (0.35 g) in 1-methyl-2-pyrrolidinone (4 ml) was treated with a solution of ethyl (Z)-2-bromomethylbut-2-enoate, (0.16 g) in 1-methyl-2-pyrrolidinone (1 ml) and stirred at ambient temperature overnight. The solution was diluted with ethyl acetate and washed with water (3×), 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 (0.368 g, 86%); νmax (CH2Cl2) 3480, 3389, 3320, 1781, 1726, 1682, 1606 and 1532 cm -1 ; δH (CDCl3) 1.30 (4H, t, J 7.1 Hz, overlapping M), 1.66 (1H, m), 1.97 (3H, d, J 7.3 Hz), 2.35 (1H, m), 3.33 and 3.64 (2H, ABq, J 18.7 Hz), 3.88 (2H, m), 4.08 (3H, s), 4.22 (2H, q, J 7.1 Hz), 4.93 (1H, m), 5.05 (3H, m), 5.80 (2H, br s, exch.), 5.99 (1H, dd, J 4.8, 9.0 Hz, collapses to d, J 4.8 Hz on exch.), 6.83 (1H, s), 7.21 (1H, q, J 7.3 Hz) and 7.73 (1H, d, J 9.0 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (580)].

Workup

  1. washwashed with water (3×), 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-04a010845c7d4669b9ed095e6c15f97a
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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