1-(Benzyloxy)-3-bromobenzene → 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole

HRID 429

Reaction equation

HRID 429 reaction equation
Brc1cccc(OCc2ccccc2)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]>Cc1cc2ccc(OC(F)(F)F)cc2n1-c1cccc(OCc2ccccc2)c1

Participants

7

Reactant 2

HCID 27566381-(Benzyloxy)-3-bromobenzeneHCID 121806692-Methyl-6-(trifluoromethoxy)-1H-indole

Product 1

HCID 592167202-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indoleYield 59.07%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

EN04773-53, _Buchwald coupling, toluene and bromide_ The indole from 4773-25, 1-(benzyloxy)-3-bromobenzene,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 100 °C for 2h. Ca 60% conversion according to LCMS (product at 2.31 min). This conversion rate seemed faster than for the corresponding aryliodide. Big bacth was performed in 4773-54.

Sources & evidence

ORD record
ord-0addbbece6dc4ca2acdd8d8c9131d423
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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