1,2-Dichloroethane → 4-(2,2-Difluoro-1-phenylethylcarbamoyl)-3-fluorophenylboronic acid

HRID 595797Notes

Reaction equation

HRID 595797 reaction equation
[B:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([F:13])[CH:5]=1)([OH:3])[OH:2].[F:14][CH:15]([F:24])[CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[NH2:17].CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CN(C=O)C>[F:14][CH:15]([F:24])[CH:16]([NH:17][C:8]([C:7]1[CH:11]=[CH:12][C:4]([B:1]([OH:2])[OH:3])=[CH:5][C:6]=1[F:13])=[O:10])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27632014-Carboxy-3-fluorophenylboronic acidHCID 452826412,2-Difluoro-1-phenylethan-1-amine

Product 1

HCID 1235349834-(2,2-Difluoro-1-phenylethylcarbamoyl)-3-fluorophenylboronic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-borono-2-fluorobenzoic acid (200 mg, 1.087 mmol), 2,2-difluoro-1-phenylethanamine (232 mg, 1.196 mmol), and DIEA (0.570 mL, 3.26 mmol) in THF (3.866 mL) and DMF (0.483 mL) was added HOAt (296 mg, 2.175 mmol) and EDC (521 mg, 2.72 mmol). After 3 h stirring at room temperature, 10% citric acid solution was added (pH ˜3) and extracted with 2-methyl THF and EtOAc (1:1). The organic layers were dried over anhydrous Na2SO4, filtered, and concentrated. The crude 4-(2,2-difluoro-1-phenylethylcarbamoyl)-3-fluorophenylboronic acid was obtained (90%) and used for the next step without purification. LCMS (m/z): 375.3 (MH+), 0.48 min.

Workup

  1. extractionextracted with 2-methyl THF and EtOAc (1:1)
  2. dry with materialThe organic layers were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-10da6daac0da476486f9959ec4a2ca54
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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