Hydrochloric Acid → HCID 66704132, compound

HRID 424786Notes

Reaction equation

HRID 424786 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.[CH3:18][O:19][C:20](=[O:32])[CH2:21][C:22]1[C:30]2C(=C[C:27](Br)=[CH:28][CH:29]=2)NC=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:40][N:41]([CH:43]=O)[CH3:42]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[CH3:18][O:19][C:20]([C:21]1[C:22]2[C:42](=[CH:27][C:28]([C:7]3[CH:6]=[CH:5][C:4]([OH:17])=[CH:3][C:2]=3[CH3:1])=[CH:29][CH:30]=2)[N:41]([CH3:40])[CH:43]=1)=[O:32]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11644701HCID 11644701, compoundHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol

Product 1

HCID 66704132HCID 66704132, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (105 mg, 0.448 mmol), (6-bromo-1H-indol-3-yl)-acetic acid methyl ester (100 mg, 0.373 mmol), tetrakis(triphenylphosphine)palladium(0) (25 mg, 0.021 mmol), DMF (1.2 mL), ethanol (0.6 mL) and 2M aqueous potassium carbonate (0.6 mL) is heated to 80° C. for 6 hours. The reaction is cooled to room temperature, diluted with water, and acidified with 1 N HCl. The resulting solution is extracted with CH2Cl2. The combined organic layers are dried over anhydrous magnesium sulfate and concentrated. The residue is purified via radial chromatography eluting with CH2Cl2. A second purification of impure fractions is performed via radial chromatography eluting with 2% MeOH—CH2Cl2 to provide (78 mg, 74%) of the title compound. LC-ES/MS m/e 296.0 (M+1).

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. extractionThe resulting solution is extracted with CH2Cl2
  3. dry with materialThe combined organic layers are dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified via radial chromatography
  6. washeluting with CH2Cl2
  7. customA second purification of impure fractions
  8. washeluting with 2% MeOH—CH2Cl2

Sources & evidence

ORD record
ord-7a91c237ac7f43c5bb9b3c3c30c09144
Source dataset
uspto-grants-2012_01
Patent number
US08106077B2

Reaction notes

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