1,2-Dichloroethane → (R)-3-fluoro-4-(1-(2-fluorophenylsulfonyl)piperidin-3-ylcarbamoyl)phenylboronic acid

HRID 595795Notes

Reaction equation

HRID 595795 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][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21]([N:24]1[CH2:29][CH2:28][CH2:27][C@@H:26]([NH2:30])[CH2:25]1)(=[O:23])=[O:22].CCN(C(C)C)C(C)C.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>C1COCC1.CN(C=O)C>[F:13][C:6]1[CH:5]=[C:4]([B:1]([OH:2])[OH:3])[CH:12]=[CH:11][C:7]=1[C:8](=[O:10])[NH:30][C@@H:26]1[CH2:27][CH2:28][CH2:29][N:24]([S:21]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[F:14])(=[O:22])=[O:23])[CH2:25]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27632014-Carboxy-3-fluorophenylboronic acidHCID 28418373(R)-1-(2-fluorophenylsulfonyl)piperidin-3-amine

Product 1

HCID 123376552(R)-3-fluoro-4-(1-(2-fluorophenylsulfonyl)piperidin-3-ylcarbamoyl)phenylboronic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-borono-2-fluorobenzoic acid (160 mg, 0.870 mmol), (R)-1-(2-fluorophenylsulfonyl)piperidin-3-amine (225 mg, 0.870 mmol), and DIEA (456 μL, 2.61 mmol) in THF (1450 μL) and DMF (1450 μL) was added HOAt (237 mg, 1.740 mmol) and EDC (417 mg, 2.175 mmol). After 3 h stirring at room temperature, the reaction mixture was extracted with EtOAc. The organic layer was washed with NaHCO3, water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo yielding (R)-3-fluoro-4-(1-(2-fluorophenylsulfonyl)piperidin-3-ylcarbamoyl)phenylboronic acid, which was used in next step reaction without purification. LCMS (m/z): 425.2 (MH+), 0.72 min.

Workup

  1. extractionthe reaction mixture was extracted with EtOAc
  2. washThe organic layer was washed with NaHCO3, water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4e5480f451d54182a4b5b1775d3e9eee
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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