Lithium Hydroxide → 1-(3-(1-Naphthyloxy)propyl)-3-((e)-2-phenylvinyl)-1h-indole-2-carboxylic acid

HRID 1013288Notes

Reaction equation

HRID 1013288 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][CH2:13][O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)[C:3]=1[C:25]([O:27]CC)=[O:26].[CH:30](/B(O)O)=[CH:31]\[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(COC)OC.[Li+].[OH-]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C>[C:15]1([O:14][CH2:13][CH2:12][CH2:11][N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2](/[CH:30]=[CH:31]/[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[C:3]2[C:25]([OH:27])=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 80711,2-DimethoxyethaneHCID 5702628Styrylboronic acidHCID 67316935Ethyl 3-bromo-1-(3-(naphthalen-1-yloxy)propyl)-1h-indole-2-carboxylate

Product 1

HCID 251016641-(3-(1-Naphthyloxy)propyl)-3-((e)-2-phenylvinyl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent

Procedure

A mixture of EXAMPLE 31C (100 mg), (E)-styrylboronic acid (39 mg), and bis(triphenylphosphine)palladium(II) dichloride (8 mg) in 7:3:3 dimethoxyethane:ethanol: 1N aqueous LiOH (2 mL) was heated under microwave conditions (CEM Discover) at 130° C. for 30 minutes The mixture was quenched with 1 NHCl and extracted with ethyl acetate. The extract was dried (Na2SO4), filtered, and concentrated. The concentrate was purified by reverse phase HPLC (Zorbax SB-C18, 20-100% acetonitrile/water/0.1% trifluoroacetic acid) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 13.59 (br, 1H), 8.24 (m, 1H), 8.15 (d, 1H), 7.94 (m, 1H), 7.87 (m, 1H), 7.69 (d, 1H), 7.59 (m, 2H), 7.53 (m, 2H), 7.46 (m, 1H), 7.40 (m, 3H), 7.28 (m, 3H), 7.21 (m 1H), 6.87 (d, 1H), 4.87 (t, 2H), 4.17 (t, 2H), 2.34 (m, 2H).

Workup

  1. customwas quenched with 1 NHCl
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extract was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrate was purified by reverse phase HPLC (Zorbax SB-C18, 20-100% acetonitrile/water/0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-5593c89ef2dd451f8b05b890483462a5
Source dataset
uspto-grants-2011_07
Patent number
US07981888B2

Reaction notes

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