Tetrahydrofuran → HCID 67342791, compound

HRID 1253912Notes

Reaction equation

HRID 1253912 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6](B(O)O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:13][O:14][C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22]Br)[CH:17]=1.C1COCC1.C([O-])([O-])=O.[K+].[K+]>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.O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH2:22][C:18]3[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=3)[C:15]([O:14][CH3:13])=[O:24])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 517981Methyl 3-(bromomethyl)benzoateHCID 27343615-Indolylboronic acid

Product 1

HCID 67342791HCID 67342791, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Indole-5-boronic acid, 193 mg (1.2 mmol) and methyl-3-(bromomethyl)benzoate, 230 mg (1.0 mmol) were added into a 100 ml round-bottomed flask containing 15 ml THF, then 50 mg Pd(PPh3)4 was added, followed by 2 ml 2M K2CO3. The mixture was stirred and heated to 80° C. under N2 protection for over 4 hours. The reaction was monitored by TLC. After the reaction was completed and the mixture was cooled to room temperature, 10 ml H2O was added and the product extracted with ethyl acetate (15 ml×3). The organic solvent was combined and dried with anhydrous Na2SO4, filtered and evaporated to dryness. The crude product was purified by chromatographic column using hexane:ethyl acetate (7:1) as eluent. 260 mg methyl 3-(1H-indol-5-ylmethyl)benzoate was obtained as a pale yellow solid, yield 48%. Saponification of the ester yielded the target compound, 8.2 mg target compound was obtained as a grey powder. Mass calculated for C16H13NO2: 251; LCMS: 252.6 (M+H)+; 1HNMR (400 MHz, DMSO-d6) δ ppm 7.78 (1H, s), 7.74 (1H, d, J=7.9 Hz), 7.50 (1H, d, J=7.3 Hz), 7.38 (2H, m), 7.29 (2H, m), 6.95 (1H, dd, J=8.5 Hz, J=1.2 Hz), 6.35 (1H, s), 4.05 (2H, s).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. extractionthe product extracted with ethyl acetate (15 ml×3)
  3. dry with materialdried with anhydrous Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by chromatographic column

Sources & evidence

ORD record
ord-38e9edbe97f34088ae6a326018f8ab53
Source dataset
uspto-grants-2013_06
Patent number
US08455516B2

Reaction notes

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