3-Bromoanisole → 1-(3-Methoxyphenyl)-2-methyl-6-(trifluoromethoxy)indole

HRID 434

Reaction equation

HRID 434 reaction equation
COc1cccc(Br)c1.Cc1cc2ccc(OC(F)(F)F)cc2[nH]1>CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C.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]>COc1cccc(-n2c(C)cc3ccc(OC(F)(F)F)cc32)c1

Participants

7

Reactant 2

HCID 169713-BromoanisoleHCID 121806692-Methyl-6-(trifluoromethoxy)-1H-indole

Product 1

HCID 184389471-(3-Methoxyphenyl)-2-methyl-6-(trifluoromethoxy)indoleYield 65.49%

Reagents, catalysts & solvents 4

HCID 23676156Sodium t-butoxideReagentHCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

EN04773-51, _Buchwald coupling,_ ** _J. Med. Chem. 2009, page 3846-3854 (exactly same reaction)._** The indole from 4773-41, 1-bromo-3-methoxybenzenee,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and ~65% conversion was observed on NMR*(see attached NMR). Reaction seems to work fine and assumed better yield than in 4773-50. This could be due to that bromides generally perform better than iodines in the Buchwald coupling. This test reaction was thrown away.

Sources & evidence

ORD record
ord-5f9307492f2b4cadaa0478f3250edc2b
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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