1,4-Dibromobenzene → Methyl 1-(4-bromophenyl)pyrrolidine-3-carboxylate

HRID 520

Reaction equation

HRID 520 reaction equation
Brc1ccc(Br)cc1.COC(=O)C1CCNC1>CC(C)(C)[O-].Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COC(=O)C1CCN(c2ccc(Br)cc2)C1

Participants

7

Reactant 2

HCID 78041,4-DibromobenzeneHCID 4114360Methyl Pyrrolidine-3-carboxylate

Product 1

HCID 83981693Methyl 1-(4-bromophenyl)pyrrolidine-3-carboxylateYield 31.6%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of methyl pyrrolidine-3-carboxylate (2.1 g, 16.26 mmol), 1,4-dibromobenzene (3.84 g, 16.26 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.372 g, 0.41 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.759 g, 1.22 mmol) and Sodium Tert-Butoxide (1.875 g, 19.51 mmol) in anhydrous toluene (60 mL) was stirred at 85 °C under nitrogen for 16 hours. The reaction was cooled to ambient temperature, diluted with Ether (100 mL) and filtered through celite. The filtrate was evaporated in vacuo to yield crude product. The crude product was purified by flash silica chromatography, elution gradient 5 to 20% EtOAc in heptane. Pure fractions were evaporated to dryness to afford methyl 1-(4-bromophenyl)pyrrolidine-3-carboxylate (1.460 g, 31.6 %) as a yellow solid.

Sources & evidence

ORD record
ord-7673f35cb6ca4307811eaa7801ce679c
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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