Ethyl Acetate → Methyl 2-(6-bromo-8-phenylimidazo[1,2-a]pyridin-2-yl)acetate

HRID 2197562Notes

Reaction equation

HRID 2197562 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5](Br)[C:6]2[N:7]([CH:9]=[C:10]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[N:11]=2)[CH:8]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C(O)C.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>[Br:2][C:3]1[CH:4]=[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:6]2[N:7]([CH:9]=[C:10]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[N:11]=2)[CH:8]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 67008341Methyl 2-(6,8-dibromoimidazo[1,2-a]pyridin-2-yl)acetate hydrochloride

Product 1

HCID 58207940Methyl 2-(6-bromo-8-phenylimidazo[1,2-a]pyridin-2-yl)acetateYield 73%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of methyl 2-(6,8-dibromoimidazo[1,2-a]pyridin-2-yl)acetate hydrochloride (0.26 g, 0.68 mmol) and phenylboronic acid (0.083 g, 0.68 mmol) in toluene (9 mL) and ethanol (0.5 mL) was bubbled nitrogen for 20 mins. The mixture was then treated with Pd(PPh3)4 (26 mg, 0.022 mmol) and K3PO4 (2 M, 1 mL, 2.0 mmol) and heated at 80° C. overnight. The reaction was cooled, poured into ethyl acetate (200 mL), washed with brine, separated, and concentrated. The residue was purified by column chromatography on silica gel using ethyl acetate in hexanes (10-25%) as eluent. The product containing fractions were concentrated to give 170 mg (73% yield) of methyl 2-(6-bromo-8-phenylimidazo[1,2-a]pyridin-2-yl)acetate as a white solid. LCMS B: 2.11 min (RT); (M+H)+=347.21 (100%), 345.21 (100%). 1H NMR, 400 MHz, CDCl3: δ 8.20 (d, J=1.6 Hz, 1 H), 7.96 (m, 2 H), 7.65 (s, 1H), 7.50-7.40 (m, 3 H), 7.33 (d, J=1.6 Hz, 1 H), 3.92 (s, 2 H), 3.75 (s, 3 H).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with brine
  3. customseparated
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel
  6. additionThe product containing fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-e675716eb1364719b390804d959fd2e2
Source dataset
uspto-grants-2012_12
Patent number
US08338604B2

Reaction notes

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