Sodium Iodide → 2,2-dimethylpropanoyloxymethyl (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 376574Notes

Reaction equation

HRID 376574 reaction equation
[C:1]([O:7][CH2:8]Br)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[I-].[Na+].[I-].[NH2:13][C:14]1[S:15][CH:16]=[C:17](/[C:19](=[N:40]/[O:41][CH3:42])/[C:20]([NH:22][C@@H:23]2[C:38](=[O:39])[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+]>CC(C)=O.C1(C)C=CC=CC=1.CN1CCCC1=O.C(OCC)(=O)C>[NH2:13][C:14]1[S:15][CH:16]=[C:17](/[C:19](=[N:40]/[O:41][CH3:42])/[C:20]([NH:22][C@@H:23]2[C:38](=[O:39])[N:25]3[C:26]([C:35]([O:37][CH2:8][O:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[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

Participants

9

Reactant 4

HCID 5238Sodium IodideHCID 30165Iodide IonHCID 15916453Bromomethyl pivalateHCID 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-carboxylate

Product 1

HCID 882588472,2-dimethylpropanoyloxymethyl (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 78.1%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Pivaloyloxymethyl bromide (247mg, 1.27mmol) and sodium iodide (247mg, 1.65mmol) in acetone (5ml) were stirred for 30 min., filtered, and the filtrate concentrated in vacuo. The resulting iodide in toluene (3ml) was added to a solution of sodium (6R,7R)-7-[2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (320mg, 0.67mmol) in N-methylpyrrolidinone (5ml). After stirring for 30 min. at room temperature, the reaction mixture was diluted with ethyl acetate, washed successively with water (x3) and brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 80% ethyl acetate in hexane to give the title compound as a yellow foam (297mg, 78%); vmax (CH2Cl2) 3387, 1786, 1752, 1735, 1686, 1605cm-1 ; δH (CDCl3, 250MHz) 1.22 (9H, s), 1.69 (1H, m), 1.98 (2H, m), 2.18 (1H, m), 3.43 and 3.62 (2H, ABq, J 18.0Hz), 3.80-3.96 (2H, m), 4.10 (3H, s), 5.08 (1H, d, J 4.7Hz), 5.19 (1H, m), 5.83-5.92 (3H, m), 6.32 (2H, br. s, exch), 7.02 (1H, s), 7.63 (1H, br. d, exch., J 8.6Hz). [Mass spectrum: +ve ion (thioglycerol) MH+ (568)].

Workup

  1. filtrationfiltered
  2. concentrationthe filtrate concentrated in vacuo
  3. washwashed successively with water (x3) and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel eluting with 80% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5f905e22526c4c4b9cbddf64a3441106
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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