7-Amino-3-methyl-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid → 7-tert.-Butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene

HRID 1660390Notes

Reaction equation

HRID 1660390 reaction equation
[NH2:1][CH:2]1[C:9](=[O:10])[N:8]2[CH:3]1[S:4][CH2:5][C:6]([CH3:14])=[C:7]2[C:11]([OH:13])=[O:12].[C:15](=O)([O:21]C(C)(C)C)[O:16][C:17]([CH3:20])([CH3:19])[CH3:18]>C(=O)(O)[O-].[Na+].O.O1CCOCC1>[C:17]([O:16][C:15]([NH:1][CH:2]1[C:9](=[O:10])[N:8]2[CH:3]1[S:4][CH2:5][C:6]([CH3:14])=[C:7]2[C:11]([OH:13])=[O:12])=[O:21])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 2

HCID 18837-Amino-3-methyl-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 128967587-tert.-Butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-eneYield 89.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

7-Amino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (371 g) is dissolved in a solution of sodium bicarbonate (307 g) in a mixture of distilled water (2 liters) and dioxane (2 liters). A solution of di-tert.-butyl carbonate (421 g) in dioxane (2 liters) is added in the course of 10 minutes. The reaction mixture is stirred for 48 hours at 25° C. The suspension obtained is concentrated under reduced pressure (20 mm Hg) at 50° C. to a residual volume of about 2 liters, and is then diluted with ethyl acetate (1 liter) and distilled water (2 liters). The aqueous phase is decanted, washed with ethyl acetate (500 cc) and acidified to pH 2 with 6 N hydrochloric acid in the presence of ethyl acetate (1500 cc). The aqueous phase is extracted with ethyl acetate (2×1 liter). The combined organic phases are washed with a saturated sodium chloride solution (2×250 cc) and dried over sodium sulphate. After filtration, the solvent is evaporated under reduced pressure (20 mm Hg) at 50° C. 7-tert.-Butoxycarbonylamino-2-carboxy-3-methyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (486 g) is obtained in the form of yellow crystals (m.p.=190° C., with decomposition).

Workup

  1. customThe suspension obtained
  2. concentrationis concentrated under reduced pressure (20 mm Hg) at 50° C. to a residual volume of about 2 liters
  3. additionis then diluted with ethyl acetate (1 liter)
  4. distillationdistilled water (2 liters)
  5. customThe aqueous phase is decanted
  6. washwashed with ethyl acetate (500 cc)
  7. extractionThe aqueous phase is extracted with ethyl acetate (2×1 liter)
  8. washThe combined organic phases are washed with a saturated sodium chloride solution (2×250 cc)
  9. dry with materialdried over sodium sulphate
  10. filtrationAfter filtration
  11. customthe solvent is evaporated under reduced pressure (20 mm Hg) at 50° C

Sources & evidence

ORD record
ord-7034206d02f2485c8963423f3e79dc86
Source dataset
uspto-grants-1981_12
Patent number
US04307230

Reaction notes

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