Sodium Iodide → 2,2-dimethylpropanoyloxymethyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(5-oxooxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 6295

Reaction equation

HRID 6295 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:41]/[O:42][CH3:43])/[C:20]([NH:22][C@@H:23]2[C:39](=[O:40])[N:25]3[C:26]([C:36]([O-:38])=[O:37])=[C:27]([CH:30]4[O:34][C:33](=[O:35])[CH2:32][CH2:31]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:41]/[O:42][CH3:43])/[C:20]([NH:22][C@@H:23]2[C:39](=[O:40])[N:25]3[C:26]([C:36]([O:38][CH2:8][O:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[O:37])=[C:27]([CH:30]4[O:34][C:33](=[O:35])[CH2:32][CH2:31]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 44310944sodium (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(5-oxooxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 1415795472,2-dimethylpropanoyloxymethyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(5-oxooxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 59.1%

Reagents, catalysts & solvents 4

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

Procedure

Pivaloyloxymethyl bromide (0.10 g, ca. 0.5 mmol) and sodium iodide (0.1 g) in acetone (1 ml) were stirred for 0.25 h, filtered and evaporated in vacuo. The iodide in toluene (0.5 ml) was added to sodium (6R,7R)-7-[2(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-[(5RS)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylate (0.124 g, 0.25 mmol) in N-methylpyrrolidone (2 ml) and stirred for 0.5 h. The reaction mixture was diluted with ethyl acetate, washed twice with water, and with brine, dried, concentrated and flash chromatographed on silica gel eluting with 80,90,100% ethyl acetate in hexane to give the title compound (86 mg, 59%), νmax (CH2Cl2) 1780, 1753, 1735, 1682, 1532, 1374, 1121, 1046 cm-1 ; δH (250 MHz, CDCl3) (9H, s), 1.9-2.2 (1H, m), 2.4-2.8 (3H, m), 3.34 and 3.64, 3.48 and 3.59 (together 2H, 2ABq, J 18.9, 18.4 Hz), 4.08 (3H, s), 5.10, 5.11 (together 1H, 2d, J 4.9 Hz), 5.35 (2H, bs), 5.5-5.95 (3H, m), 6.00, 6.10 (together 1H, 2dd, J 9, 4.9 Hz), 6.85, 6.87 (together 1H, 2s), 7.52, 7.54 (together 1H, 2d, J 9 Hz); [mass spectrum: +ve ion (3-nitrobenzyl alcohol-sodium acetate) MH+(582) MNa+(604)].

Workup

  1. filtrationfiltered
  2. customevaporated in vacuo
  3. washwashed twice with water
  4. dry with materialwith brine, dried
  5. concentrationconcentrated
  6. customflash chromatographed on silica gel eluting with 80,90,100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-25dcd8cb6bae4c88a76e6afa5f16ed75
Source dataset
uspto-grants-1993_09
Patent number
US05246926

Linked notes

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