Ethyl bromoacetate → Ethyl 2-(quinoxalin-6-YL)acetate

HRID 655209Notes

Reaction equation

HRID 655209 reaction equation
Cl.[N:2]1[C:7]2[CH:8]=[CH:9][C:10](B(O)O)=[CH:11][C:6]=2[N:5]=[CH:4][CH:3]=1.C1(P(C2C3C(=CC=CC=3)C=CC=2)C2C3C(=CC=CC=3)C=CC=2)C2C(=CC=CC=2)C=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCCC1>[CH2:59]([O:58][C:56](=[O:57])[CH2:55][C:10]1[CH:11]=[C:6]2[C:7](=[CH:8][CH:9]=1)[N:2]=[CH:3][CH:4]=[N:5]2)[CH3:60]

Participants

8

Reactant 4

HCID 7748Ethyl bromoacetateHCID 62657Potassium Phosphate, TribasicHCID 271443Tri(naphthalen-1-yl)phosphaneHCID 45073595Quinoxalin-6-ylboronic acid hydrochloride

Product 1

HCID 68705540Ethyl 2-(quinoxalin-6-YL)acetateYield 18.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A vial under nitrogen atmosphere was charged with benzopyrazine-6-boronic acid hydrochloride (500 mg, 2.38 mmol), palladium (II) acetate (16 mg, 0.071 mmol), tri-1-naphthylphosphine (88 mg, 0.214 mmol), potassium phosphate tribasic (2.52 g, 11.9 mmol), and tetrahydrofuran (10 mL). Ethyl 2-bromoacetate (0.315 mL, 2.85 mmol) was then added and the reaction mixture was stirred at reflux for 6 h. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic layers were adsorbed on silica gel. Purification on silica gel with 0-100% gradient of ethyl acetate in hexane provided 96 mg of product as a dark yellow oil. 1H NMR 500 MHz (DMSO) δ 1.20 (t, 3H), 3.99 (s, 2H), 4.11 (q, 2H), 7.79 (dd, 1H), 8.01 (d, 1H), 8.06 (d, 1H), 8.94 (d, 2H); MS (m/z) 217 [M+H+]+.

Workup

  1. temperatureat reflux for 6 h
  2. extractionthe mixture was extracted with ethyl acetate (3×)
  3. customPurification on silica gel with 0-100% gradient of ethyl acetate in hexane

Sources & evidence

ORD record
ord-14ddcff113764a1e816948d53cd80c30
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

Loading…