Improved Synthesis of Buprenorphine from Thebaine and/or Oripavine <i>via</i> Palladium‐Catalyzed N‐Demethylation/Acylation and/or Concomitant O‐Demethylation
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract An improved preparation of buprenorphine via palladium‐catalyzed N‐demethylation/acylation is reported. Three routes were investigated and compared in overall yield. The first involved N‐demethylation/acylation of an advanced intermediate obtained from thebaine followed by hydrolysis of the N ‐acetamide and alkylation with cyclopropylmethyl bromide and/or reduction of the N ‐acetyl group with the Schwartz reagent followed by N‐alkylation. The second route employed cyclopropylcarboxylic acid anhydride in the N‐demethylation/acylation protocol and subsequent reduction of the cyclopropylcarboxamide by either lithium aluminum hydride or under hydrosilylation conditions. Both of these routes originated in thebaine and therefore required O‐demethylation as a final step. The third route employed an N‐demethylation/acylation sequence starting from oripavine rather than thebaine, thus avoiding the O‐demethylation. The routes are compared for overall efficiency and experimental and spectral data are provided for all new compounds.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it