3-((Acetyloxy)methyl)-7-amino-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid → 3-[(Acetyloxy)methyl]-7-[[(2,3-dihydro-5-benzofuranyl)-hydroxyacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 904022Notes

Reaction equation

HRID 904022 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]2[O:13][CH2:12][CH2:11][C:10]=2[CH:14]=1)[C:3]([OH:5])=O.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.ClC(OCC(C)C)=O.[C:35]([O:38][CH2:39][C:40]1[CH2:47][S:46][CH:45]2[N:42]([C:43](=[O:49])[CH:44]2[NH2:48])[C:41]=1[C:50]([OH:52])=[O:51])(=[O:37])[CH3:36].C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.CCOCC.C(N(CC)CC)C.C1COCC1>[C:35]([O:38][CH2:39][C:40]1[CH2:47][S:46][CH:45]2[N:42]([C:43](=[O:49])[CH:44]2[NH:48][C:3](=[O:5])[CH:2]([C:6]2[CH:7]=[CH:8][C:9]3[O:13][CH2:12][CH2:11][C:10]=3[CH:14]=2)[OH:1])[C:41]=1[C:50]([OH:52])=[O:51])(=[O:37])[CH3:36]

Participants

11

Reactant 5

HCID 137293-((Acetyloxy)methyl)-7-amino-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 233358212-(2,3-Dihydrobenzofuran-5-yl)-2-hydroxyacetic acid

Product 1

HCID 233358483-[(Acetyloxy)methyl]-7-[[(2,3-dihydro-5-benzofuranyl)-hydroxyacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

α-Hydroxy-(2,3-dihydro-5-benzofuranyl)acetic acid (10 mmole) triethylamine (10 mmole) and bistrimethylsilylacetamide (BSA) (10 mmole) are added to 50 ml of THF and refluxed for two hours. The reaction mixture is cooled to about -10° C. and 10 mmole of isobutyl chloroformate is added dropwise. After 30 minutes at -10° C., 10 mmole of 3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid in 50 ml of water--20 ml of THF containing 10 mmole of triethylamine is added dropwise to the cooled reaction mixture. The temperature is maintained between -10° C. and 0° C. during the addition. The reaction mixture is allowed to come to room temperature very slowly. About 50 cc of saturated aqueous sodium bicarbonate and 100 ml of water are added to the reaction mixture. This mixture is treated several times with ether which is then discarded. The aqueous phase is layered with ethyl acetate and the pH of the aqueous solution is adjusted to 1.5. The ethyl acetate is then separated from the aqueous phase, dried over magnesium sulfate, filtered and evaporated to give the title compound.

Workup

  1. temperaturerefluxed for two hours
  2. temperatureThe temperature is maintained between -10° C. and 0° C. during the addition
  3. customto come to room temperature
  4. customThe ethyl acetate is then separated from the aqueous phase
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-465e82eacbed49e6b67aed423f7e4b3c
Source dataset
uspto-grants-1980_10
Patent number
US04229575

Reaction notes

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