6-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid → 6-[[[3-(Azidomethyl)-4-hydroxyphenyl]hydroxyacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

HRID 2049228Notes

Reaction equation

HRID 2049228 reaction equation
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([CH2:13][N:14]=[N+:15]=[N-:16])[CH:7]=1)[C:3]([OH:5])=O.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(OC(Cl)=O)C(C)C.[NH2:37][CH:38]1[C:44](=[O:45])[N:43]2[CH:39]1[S:40][C:41]([CH3:50])([CH3:49])[CH:42]2[C:46]([OH:48])=[O:47].C(=O)(O)[O-].[Na+]>O1CCCC1.O.C(N(CC)CC)C>[N:14]([CH2:13][C:8]1[CH:7]=[C:6]([CH:2]([OH:1])[C:3]([NH:37][CH:38]2[C:44](=[O:45])[N:43]3[CH:39]2[S:40][C:41]([CH3:50])([CH3:49])[CH:42]3[C:46]([OH:48])=[O:47])=[O:5])[CH:11]=[CH:10][C:9]=1[OH:12])=[N+:15]=[N-:16]

Participants

9

Reactant 5

HCID 1626-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acidHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 20344779alpha-Hydroxy-3-(azidomethyl)-4-hydroxybenzeneacetic acid

Product 1

HCID 203447646-[[[3-(Azidomethyl)-4-hydroxyphenyl]hydroxyacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
-10 °C

Procedure

α-Hydroxy-3-(azidomethyl)-4-hydroxybenzeneacetic acid (30 mmole) is dissolved in tetrahydrofuran (THF). To this solution is added (45 mmole) bistrimethylsilylacetamide and (30 mmole) triethylamine. The mixture is refluxed for 2 hours after which the reaction mixture is cooled to about -10° C. and 30 mmole of isobutylchloroformate is added dropwise. After 30 mixtures at -10° C., 30 mmole of 6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylic acid in 50 ml of THF-20 ml of water containing 30 mmole of triethylamine is added to the previously prepared solution at -10° C. The temperature of the reaction mixture is allowed to warm from -10° C. to room temperature over one hour. About 50 ml of saturated sodium bicarbonate and 100 ml of water are added to the reaction mixture which is twice extracted with ether. The aqueous phase is layered with ethyl acetate and the pH is adjusted to 1.5 by the addition of hydrochloric acid. The ethyl acetate is separated from the aqueous phase, dried over sodium sulfate, filtered and evaporated to give the title compound.

Workup

  1. temperatureThe mixture is refluxed for 2 hours after which the reaction mixture
  2. temperatureto warm from -10° C. to room temperature over one hour
  3. extractionis twice extracted with ether
  4. additionthe pH is adjusted to 1.5 by the addition of hydrochloric acid
  5. customThe ethyl acetate is separated from the aqueous phase
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-4ee374c7949b40f2b985cf030f5c145b
Source dataset
uspto-grants-1980_04
Patent number
US04197240

Reaction notes

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