1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(4-Bromophenyl)piperazin-1-yl](2,2-difluorocyclopropyl)methanone

HRID 340631ノート

反応式

HRID 340631 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:14][C:15]1([F:21])[CH2:17][CH:16]1[C:18](O)=[O:19].CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C.C(O)C.CCCCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:18]([CH:16]3[CH2:17][C:15]3([F:21])[F:14])=[O:19])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27356291-(4-Bromophenyl)piperazineHCID 27828232,2-Difluorocyclopropane-1-carboxylic acid

生成物 1

HCID 86692009[4-(4-Bromophenyl)piperazin-1-yl](2,2-difluorocyclopropyl)methanone

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒HCID 8900Heptane溶媒

反応条件

温度
50 °C

実験手順

To a solution of 1-(4-bromophenyl)piperazine (2.53 g, 10.5 mmol) in DMF (10 mL) was added 2,2-difluorocyclopropanecarboxylic acid (1.92 g, 15.7 mmol) 1H-benzotriazol-1-ol (2.84 g, 21.0 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide (3.26 g, 21.0 mmol) and DIEA (7.31 mL, 42.0 mmol). The resulting mixture was stirred at 50° C. for 1 h. The reaction mixture was then quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and concentrated in vacuo. Purification by chromatography on silica gel (0 to 75% EtOAc in hexanes, then 75 to 100% EtOAc in hexanes) provided the racemic compound. The racemate was then dissolved in 10% ethanol in heptane and the enantiomers were separated on an OD chiral column by eluting column with 30% ethanol in heptane. The first eluting peak was defined as enantiomer A and the second eluting peak was defined as enantiomer B. LCMS m/z 346.8 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 7.37 (d, J=9.0 Hz, 2 H),6.80 (d, J=9.0 Hz, 2 H), 4.00-3.93 (m, 1 H),3.84-3.61 (m, 3 H),3.31-3.02 (m, 4 H),2.60-2.50 (m, 1 H),2.23-2.11 (m, 1 H),1.75-1.64 (m, 1 H).

後処理

  1. customThe reaction mixture was then quenched with saturated ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. customPurification by chromatography on silica gel (0 to 75% EtOAc in hexanes
  5. custom75 to 100% EtOAc in hexanes) provided the racemic compound
  6. customthe enantiomers were separated on an OD chiral column
  7. washby eluting column with 30% ethanol in heptane

出典と根拠

ORDレコード
ord-b0ee99ca52a14c3397a245bbd1b807a5
出典データセット
uspto-grants-2014_11
特許番号
US08895583B2

反応ノート

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