Acetyl bromide → benzhydryl (6R,7R)-3-methyl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1105785

Reaction equation

HRID 1105785 reaction equation
C1([CH:7]([O:14][C:15]([C@@H:17]2[N:21]3[C:22](=[O:35])[C@@H:23]([NH:24][C:25](=[O:34])[CH2:26][O:27]C4C=CC=CC=4)[C@H:20]3[S@@:19](=O)[C:18]2([CH3:38])[CH3:37])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)C=CC=CC=1.[C:39](Br)(=O)[CH3:40]>N1C=CC=CC=1>[C:8]1([CH:7]([O:14][C:15]([C:17]2[N:21]3[C:22](=[O:35])[C@@H:23]([NH:24][C:25](=[O:34])[CH2:26][O:27][C:40]4[CH:39]=[CH:37][CH:18]=[CH:17][CH:15]=4)[C@H:20]3[S:19][CH2:37][C:18]=2[CH3:38])=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 10482Acetyl bromideHCID 56631626Benzhydryl penicillin V sulfoxide, (S)-

Product 1

HCID 112091benzhydryl (6R,7R)-3-methyl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

(1S,3S,5R,6R) 2,2-Dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide diphenylmethyl ester (55.06 gms, 100.00 mmoles) was dissolved in sieve-dried, peroxide-free dioxane (550 mls) at 25° C. with good agitation. To this solution, in order, were added pyridine (24.21 mls, 23.73 gms, 300.00 mmmoles), acetyl bromide (1.48 mls, 2.46 gms, 20.00 mmoles) and methylsilyl triisocyanate (89% pure, 21.30 mls, 25.34 gms, 133.33 mmoles). The slurry was heated to reflux (ca 100° C.) for 4 hours. The reaction mixture was then cooled to 25° C. and filtered, with the clear yellow filtrate being concentrated in vacuo at 50° C. to a highly viscous oil. The oil was dissolved in hot 2-propanol (~80° C., 3000 mls), filtered, and allowed to cool to 25° C. The slurry was cooled to 0°-5° C. for 2 hours, filtered, and washed with 2-propanol (0°-5° C., 400 mls), and oven-dried at 45° C. to constant weight. Yield: 38.6 gms, 75% of white crystalline title compound. The 80 MHz H' NMR spectrum was clean and consistent for the desired structure.

Workup

  1. customin sieve-dried
  2. customat 25° C.
  3. temperatureThe slurry was heated
  4. temperatureto reflux (ca 100° C.) for 4 hours
  5. filtrationfiltered, with the clear yellow filtrate
  6. concentrationbeing concentrated in vacuo at 50° C. to a highly viscous oil
  7. dissolutionThe oil was dissolved in hot 2-propanol (~80° C., 3000 mls)
  8. filtrationfiltered
  9. temperatureto cool to 25° C
  10. temperatureThe slurry was cooled to 0°-5° C. for 2 hours
  11. filtrationfiltered
  12. washwashed with 2-propanol (0°-5° C., 400 mls)
  13. customoven-dried at 45° C. to constant weight

Sources & evidence

ORD record
ord-82c2dd028bff4a3da91e9f8f27f0cc2d
Source dataset
uspto-grants-1982_01
Patent number
US04310459

Linked notes

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