Cesium carbonate → N-(4-(4-chloro-2-fluorophenyl)-5-formylpyridin-2-yl)acetamide

HRID 870941Notes

Reaction equation

HRID 870941 reaction equation
Cl[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][N:5]=[C:4]([NH:10][C:11](=[O:13])[CH3:12])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[C:17]([F:24])[CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C1COCC1.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>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2[C:7]([CH:8]=[O:9])=[CH:6][N:5]=[C:4]([NH:10][C:11](=[O:13])[CH3:12])[CH:3]=2)=[C:17]([F:24])[CH:16]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86695931N-(4-chloro-5-formylpyridin-2-yl)acetamide

Product 1

HCID 86695932N-(4-(4-chloro-2-fluorophenyl)-5-formylpyridin-2-yl)acetamideYield 60%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of N-(4-chloro-5-formylpyridin-2-yl)acetamide (3 g, 15.11 mmol), (4-chloro-2-fluorophenyl)boronic acid (2.63 g, 15.11 mmol), cesium carbonate (9.84 g, 30.2 mmol) in a mixture of water (8 mL) and THF (25 mL) was added Pd(PPh3)4 (19.19 mg, 0.017 mmol) and the reaction was heated to 85° C. for 12 h. The reaction mixture was diluted with water and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, brine, dried over sodium sulphate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using hexane/ethyl acetate as eluant yielding N-(4-(4-chloro-2-fluorophenyl)-5-formylpyridin-2-yl)acetamide (2.8 g, 9.01 mmol, 60% yield) as an off-white solid. LCMS (ESI) m/e 291.0 [(M)−, calcd for C14H9ClFN2O2 291.0] LC/MS retention time (method A): tR=1.69 min; 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 9.84 (d, J=Hz, 1H), 8.88 (s, 1H), 8.13 (s, 1H), 7.61 (dd, J=2.00, 10.00 Hz, 1H), 7.46-7.48 (m, 2H), 2.11 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washThe combined organic layers were washed with water, brine
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-614786ce3e6a45b2b27ba75940cdc952
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

Loading…