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Buchwald–Hartwig amination: 2-[(5-Bromo-3-methoxy-2-pyridinyl)carbonyl]cyclopropanecarboxylic acid ethyl ester → (1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acid

29% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 recorded runs making this product; all of them are compared below.

verified record, 29% yield recorded, Not balanced as written, From experimental reaction archive

Reagents, catalysts and solvents are in the table below.

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The atoms, from reactants to products

COCCCNCCCCCCCCFFFCCCFCNCCOCCCCOOCCBr
Reactants · 1/6
breakingformingbond order changesmapped atom that changes

Drawn from the record's atom map: which bonds break and which form between the reactants and products the source listed. It shows a change in connectivity, not a simulated trajectory and not a mechanism.

What was in the flask

RoleSpeciesFormulaYield
Reactant2-[(5-Bromo-3-methoxy-2-pyridinyl)carbonyl]cyclopropanecarboxylic acid ethyl esterC₁₃H₁₄BrNO₄—
Reactant2-fluoro-N-(2-methylpropyl)-5-(trifluoromethyl)anilineC₁₁H₁₃F₄N—
ReagentCesium carbonateCCs₂O₃—
CatalystBinap, (A+-)-C₄₄H₃₂P₂—
CatalystPalladium (II) acetateC₄H₈O₄Pd—
SolventTolueneC₇H₈—
Product(1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acidC₂₂H₂₂F₄N₂O₄29.09%

The equation does not balance as written. That is usual for an experimental record: the source listed what it put in and what it measured, not a stoichiometric equation.

Conditions

Temperature
110 °C

Only the dimensions the source stated are listed. Anything absent here was not recorded, and it is not inferred from what the class usually needs.

Yield

  • 29% of (1S,2S)-2-[(5-{[2-Fluoro-5-(trifluoromethyl)phenyl](2-methylpropyl)amino}-3-methoxypyridin-2-yl)carbonyl]cyclopropanecarboxylic acid.

Every recorded run making this product

2 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.

ReactantsCatalystReagentsSolventTemp.TimeYield
2-[(5-Bromo-3-methoxy-2-pyridinyl)carbonyl]cyclopropanecarboxylic acid ethyl ester; 2-fluoro-N-(2-methylpropyl)-5-(trifluoromethyl)anilineBinap, (A+-)-; Palladium (II) acetateCesium carbonateToluene110 °C—29% (this run)
(6S)-2-(2-chloro-5-methylpyrimidin-4-yl)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-8-one; 2-Methyl-2H-pyrazol-3-ylamineBinap, (A+-)-; Palladium (II) acetateCesium carbonatenone listed110 °C—16%

Every value is as the source recorded it. A run with no yield was reported without one, and nothing here is averaged, modelled or filled in.

Procedure

Copied from the source record, unedited

(allt satsas i Toluen, N2 bubblar) start 09-jun-2014 19:51:32 +0200. LCMS-1 1600 nästa em ser bra ut, hittar inga SM, får svalna - bryter. Späder med 30 ml etoac, filtrerar genom SiO plugg, evap. evap två gånger ur 30 ml THF, LCMS-2 visar P 10-jun-2014 19:15:25 +0200 löser i 20 ml THF, 10 ml MeOH, adderar LiOH(758 mg löst i 20 ml aq) - lösning, rör rt. Kl 1951 kör LCMS-3, ser riktigt bra ut, inga SM kvar ser det ut som. Ser ingen substitution F mot MeO. Kl 20.20 quench med 2 ml HOAc, evap hårt, m=5.0 g - till SSL. 16-jun-2014 11:32:38 +0200 nu fått åter 1.4 g dygt från SSL samt även dess enantiomer. Tar det via pulvret och kör HNMR (3.5 mg i DMSO). Visar rester från upprening, sätter kl 12.07 på indunstaren med fullt vakuum 60 grC badT samt kolsyreis/aceton kylning få förlaget. Går fram

The source

This record comes from experimental reaction archive (ord-77fa1d8a9ea647299df5929297f3aa17). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-77fa1d8a9ea647299df5929297f3aa17 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.

    experimental record · quality medium · source

experimental reaction record.

How to read this record

This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.

The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.

Where to next

More Buchwald–Hartwig amination records

Other runs of this class, one page per distinct transformation.

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