Ethanol → methyl 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylate

HRID 1054703Notes

Reaction equation

HRID 1054703 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[C:4]([O:12][CH3:13])[CH:3]=1.[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][NH:21]2)=[CH:17][C:16]=1B1OCC(C)(C)CO1.C(O)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCCC1>[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][NH:21]2)=[CH:17][C:16]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylateHCID 866987012-(4-Bromo-2-methoxyphenyl)propan-2-ol

Product 1

HCID 86698700methyl 6-chloro-5-(4-(2-hydroxypropan-2-yl)-3-methoxyphenyl)-1H-indole-3-carboxylateYield 60.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid.

Workup

  1. customThe reaction was evacuated
  2. additionback filled with nitrogen (3×)
  3. temperatureThe reaction was then cooled to room temperature
  4. filtrationfiltered through a pad of celite
  5. washwashing with ethyl acetate
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified via column chromatography (0-40% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-6e7bd46b8a2f48d1b974d67c9923667c
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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