Pilot Plant Preparation of <i>tert-</i>Butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate, An Intermediate of Novel Antiarteriosclerotics, Via a Safe, Scalable Reformatsky-Type Reaction

Reported here is a safe, scalable process via a Reformatsky-type reaction of iminium salt (<b>4</b>) followed by Red-Al reduction giving <i>tert</i>-butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate (<b>6</b>), an intermediate of novel antiarteriosclerotics (<b>1</b>). The key points of this safe process are the use of trifluoroacetic acid (TFA) for the iminium salt formation, vigorous stirring for the Reformatsky reaction, and slow addition of methyl bromoacetate. Pilot manufacturing on the 500 L scale was achieved

Simple linear regression analysis of NAb with age, sex, comorbidity, and disease severity at 2M, 6M, and 12M.

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Simple linear regression analysis of anti-NC-Ab with age, sex, comorbidity, and disease severity at 2M, 6M, and 12M.

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Additional file 6 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 6. Admission to intensive care unitand use of invasive mechanical ventilationof bacterial respiratory infection with coronavirus disease 2019

Additional file 1 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 1. Identification of organisms in ventilator-associated pneumoniacase

Additional file 4 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 4. Details of respiratory secondary infection

Additional file 5 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 5. Association of anti-IL-6 receptor antibody use with incidence of secondary infection and death

Additional file 8 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 8. Proportion of thrombosis and myocardial injury in bacterial respiratory co-infection and secondary infection with coronavirus disease 2019

Additional file 3 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 3. Neutrophil-lymphocyte ratioas a predictor of co-infection in steroid and non-steroid user

Additional file 2 of Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Additional file 2. Evaluation of white blood cells, neutrophils, lymphocytes, neutrophil-lymphocyte ratio, C-reactive protein, and procalcitonin on admission as predictors of respiratory bacterial co-infection based on the area under the curv