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

HRID 595797

반응식

HRID 595797 반응식
[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

참가 물질

9

반응물 6

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-10da6daac0da476486f9959ec4a2ca54
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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