Iodomethyl pivalate → 3-[(1-Methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-2-pivaloyloxymethoxycarbonyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene

HRID 258781Notes

Reaction equation

HRID 258781 reaction equation
[C:1]([O:7][CH2:8]I)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Na].[C:11]([C:14]1[N:15]2[CH:18]([S:19][CH2:20][C:21]=1[CH2:22][S:23][C:24]1[N:28]([CH3:29])[N:27]=[N:26][N:25]=1)[CH:17]([NH:30][C:31](=[O:39])[CH2:32][C:33]1[S:34][C:35](=[O:38])[S:36][CH:37]=1)[C:16]2=[O:40])([OH:13])=[O:12]>CN(C)C=O>[CH3:29][N:28]1[C:24]([S:23][CH2:22][C:21]2[CH2:20][S:19][CH:18]3[N:15]([C:16](=[O:40])[CH:17]3[NH:30][C:31](=[O:39])[CH2:32][C:33]3[S:34][C:35](=[O:38])[S:36][CH:37]=3)[C:14]=2[C:11]([O:13][CH2:8][O:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[O:12])=[N:25][N:26]=[N:27]1

Participants

5

Reactant 3

HCID 104401Iodomethyl pivalateHCID 5360545SodiumHCID 214264602-Carboxy-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene

Product 1

HCID 214264653-[(1-Methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-2-pivaloyloxymethoxycarbonyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-eneYield 30.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of iodomethyl pivalate (8.65 g.) in dimethylformamide (70 cc.) is added to a solution of the sodium salt of 2-carboxy-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (18.2 g.) in dimethylformamide (115 cc.) over the course of 15 minutes, whilst maintaining the temperature at 5° C. The mixture is allowed to react for one hour at 5° C. and is then concentrated to dryness under reduced pressure (0.5 mm Hg). The residue is taken up in ethyl acetate (500 cc.). The mixture is washed successively with water (600 cc.), a saturated aqueous sodium bicarbonate solution (500 cc.) and water (900 cc.). It is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg). The residue obtained is chromatographed on silica (450 g.), elution being carried out successively with a mixture of cyclohexane and ethyl acetate (6/4 by volume) (1 liter) and then with a mixture of cyclohexane and ethyl acetate (4/6 by volume) (4 liters). The eluates are concentrated to dryness under reduced pressure (20 mm Hg). A residue (12.7 g.) is obtained in the form of a frothy solid which is crystallised from a mixture of ethyl acetate and ether (1/1 by volume) (120 cc.). A white crystalline product (7.4 g.) is obtained, which when dried at 30° C. under 0.5 mm Hg retains about 3% of ethyl acetate. The product is treated overnight with water (250 cc.) while stirring and the crystals are filtered off and then dried (35° C.-0.5 mm Hg). 3-[(1-Methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-2-pivaloyloxymethoxycarbonyl-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (6.6 g.), m.p. 100° C. is thus obtained. [α]D20 = -21.6° ± 0.8° (c= 1, dimethylformamide).

Workup

  1. customto react for one hour at 5° C.
  2. concentrationis then concentrated to dryness under reduced pressure (0.5 mm Hg)
  3. washThe mixture is washed successively with water (600 cc.)
  4. dry with materialIt is dried over sodium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (20 mm Hg)
  6. customThe residue obtained
  7. customis chromatographed on silica (450 g.), elution
  8. additionbeing carried out successively with a mixture of cyclohexane and ethyl acetate (6/4 by volume) (1 liter)
  9. additionwith a mixture of cyclohexane and ethyl acetate (4/6 by volume) (4 liters)
  10. concentrationThe eluates are concentrated to dryness under reduced pressure (20 mm Hg)
  11. customA residue (12.7 g.) is obtained in the form of a frothy solid which
  12. customis crystallised from a mixture of ethyl acetate and ether (1/1 by volume) (120 cc.)
  13. customA white crystalline product (7.4 g.) is obtained
  14. customwhich when dried at 30° C. under 0.5 mm Hg
  15. additionThe product is treated overnight with water (250 cc.)
  16. filtrationthe crystals are filtered off
  17. customdried (35° C.-0.5 mm Hg)

Sources & evidence

ORD record
ord-382320169c80429085012f3a31d8a43d
Source dataset
uspto-grants-1977_07
Patent number
US04034090

Reaction notes

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