Water → HCID 86583642, compound

HRID 1698058Notes

Reaction equation

HRID 1698058 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[C:5]2[CH2:17][C:18]#[N:19].[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([CH2:17][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:3]=2)[N:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=1)#[N:19]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 86583643HCID 86583643, compound

Product 1

HCID 86583642HCID 86583642, compoundYield 45.1%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-Bromo-3-cyanomethyl-indole-N-acetic acid, ethyl ester (1.0 g, 3.1 mmol) and phenylboronic acid (0.418 g, 3.4 mmol) were dissolved in anhydrous DME at room temperature under a nitrogen atmosphere and treated with Pd(OAc)2 (2.1 mg, 0.0093 mmol) and PPh3 (7.4 mg, 0.028 mmol). This mixture was heated to reflux and 2 M Na2CO3 (3.11 mL, 6.2 mmol) was added via syringe. After 12 h, the mixture was cooled to room temperature and added to H2O (50 mL). The resultant mixture was extracted with EtOAc (2×, 100 mL) and the organics were combined and washed with a sat'd aqueous NaCl solution, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by SiO2 flash chromatography (heptane to 1:1 heptane/EtOAc) to give the desired material as a white solid (445 mg, 45%); 1H NMR (DMSO-d6, 300 MHz) δ 7.64-7.74 (m, 4H), 7.39-7.44 (m, 4H), 7.29-7.34 (m, 1H), 5.20 (s, 2H), 4.15 (q, J=7.2 Hz, 2H), 4.08 (s, 2H), 1.20 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux
  3. extractionThe resultant mixture was extracted with EtOAc (2×, 100 mL)
  4. washwashed with a sat'd aqueous NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by SiO2 flash chromatography (heptane to 1:1 heptane/EtOAc)

Sources & evidence

ORD record
ord-9c7c3fc849834ab482f102b9d4f65a7f
Source dataset
uspto-grants-2012_04
Patent number
US08163932B2

Reaction notes

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