Azide → HCID 86757877, compound

HRID 278285Notes

Reaction equation

HRID 278285 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([CH:17]=[CH2:18])[CH2:9][C:10](=[O:16])[CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:6][CH:7]=1.C(NC1C=CC(S([N:32]=[N+:33]=[N-])(=O)=O)=CC=1)(=O)C.[N-]=[N+]=[N-].C(NC1C=CC(S([NH-])(=O)=O)=CC=1)(=O)C>C(N(CC)CC)C.ClCCCl>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([CH:17]=[CH2:18])[CH2:9][C:10](=[O:16])[C:11](=[N+:32]=[N-:33])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 33558AzideHCID 51291854-Acetamidobenzenesulfonyl azideHCID 9899706HCID 9899706, compoundHCID 86757879HCID 86757879, compound

Product 1

HCID 86757877HCID 86757877, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
21 °C

Procedure

A 50 L, 4-necked round bottom flask, equipped with mechanical stirrer, thermocouple, addition funnel, nitrogen inlet, and steam pot, was charged with a solution of methyl (5S)-5-(3-fluorophenyl)-3-oxohept-6-enoate 8 (8823 g of solution, 1300 g of ketoester in 1,2-dichloroethane). Additional 1,2-dichloroethane (7 L) was charged to the flask, followed by 4-acetamidobenzenesulfonyl azide (1.25 kg). The solution was heated from about 18° C. to 21° C. with steam. (Note: the dissolution of azide was endothermic.) Triethylamine (2.17 L) was added over 40 min with water bath cooling to maintain a temperature of 19-23° C. The reaction was stirred at 18-23° C. for approximately 9 h. The reaction was mildly exothermic. The reagent product, 4-acetamidobenzenesulfonyl amide, began to precipitate from the reaction during the addition of triethylamine and eventually formed a thick slurry. The reaction was followed by HPLC and was judged complete when the amount of starting material was <0.5%. When completed, the reaction mixture was filtered, and the cake was washed four times with 1,2-dichloroethane (3×2 L displacement washes, 1×1 L slurry wash). The filtrate and washes were combined and extracted with cold (5-10 C) 2N HCl (7.4 L). The extraction was exothermic and was done in a 50 L extractor with cooling to maintain a temperature of 20-22° C. The pH of the aqueous phase was 1.0. The organic layer was extracted twice with water (2×7 L). The organic extract was charged to a 50 L, 4-necked round bottom flask, equipped with mechanical stirrer, thermocouple, nitrogen inlet, and stopper. The solution was dried for 4 h with sodium sulfate (1 kg). The organic solution was passed through a 5 μ inline filter. The final weight of organic solution was 25.6 kg. Final yield of 9 was >95%.

Workup

  1. customA 50 L, 4-necked round bottom flask, equipped with mechanical stirrer
  2. additionthermocouple, addition funnel, nitrogen inlet
  3. temperatureThe solution was heated from about 18° C. to 21° C. with steam
  4. temperaturecooling
  5. customto precipitate from the reaction during the addition of triethylamine
  6. customeventually formed a thick slurry
  7. filtrationthe reaction mixture was filtered
  8. washthe cake was washed four times with 1,2-dichloroethane (3×2 L displacement washes, 1×1 L slurry wash)
  9. extractionextracted with cold (5-10 C) 2N HCl (7.4 L)
  10. extractionThe extraction
  11. temperaturewith cooling
  12. temperatureto maintain a temperature of 20-22° C
  13. extractionThe organic layer was extracted twice with water (2×7 L)
  14. extractionThe organic extract
  15. additionwas charged to a 50 L, 4-necked round bottom flask
  16. customequipped with mechanical stirrer
  17. dry with materialThe solution was dried for 4 h with sodium sulfate (1 kg)
  18. filtrationfilter

Sources & evidence

ORD record
ord-6565dff2ffdb41dc8c227957f965e661
Source dataset
uspto-grants-2002_03
Patent number
US06358979B1

Reaction notes

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