N-bromobutanimide → 3-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-chlorobenzoic acid

HRID 44085Notes

Reaction equation

HRID 44085 reaction equation
C1C(=O)N([Br:8])C(=O)C1.[Cl:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][C:11]=1[C:19]1[CH:20]=[C:21]2[CH:27]=[C:26]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[O:25][C:22]2=[N:23][CH:24]=1>C1COCC1.CCOC(C)=O>[Br:8][C:27]1[C:21]2[C:22](=[N:23][CH:24]=[C:19]([C:11]3[CH:12]=[C:13]([CH:17]=[CH:18][C:10]=3[Cl:9])[C:14]([OH:16])=[O:15])[CH:20]=2)[O:25][C:26]=1[C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimide3×HCID 672170504-Chloro-3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid

Product 1

HCID 672176753-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-chlorobenzoic acidYield 94.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

NBS (29.0 mg, 0.163 mmol) was added to a stirring solution of 4-chloro-3-(2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid (50 mg, 0.136 mmol) in THF (4.5 mL) at room temperature. It was allowed to stir for 1 hour. An additional portion of NBS (29 mg, 0.16 mmol) was added it was allowed to stir for 1 hour after which another portion of NBS (29 mg, 0.16 mmol) was added and the reaction was allowed to stir overnight. The mixture was diluted with EtOAc and washed with 10% NaHSO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and triturated with DCM to give the expected product 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-chlorobenzoic acid (57 mg, 0.128 mmol, 94% yield) consistent by LCMS and NMR. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.48 (1H, d, J=2.14 Hz), 8.19-8.24 (2H, m), 8.17 (1H, d, J=2.14 Hz), 7.99-8.05 (2H, m), 7.79 (1H, d, J=8.24 Hz), 7.46-7.52 (2H, m). LC-MS retention time: 1.29 min; m/z (MH+): 447. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. additionwas added
  2. stirringto stir overnight
  3. washwashed with 10% NaHSO3
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customtriturated with DCM

Sources & evidence

ORD record
ord-dba3add8755c434cafc1c4397cd01f83
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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