Dimethylformamide → HCID 57633767、化合物

HRID 2240886ノート

反応式

HRID 2240886 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH2:10][CH:11]([CH3:15])[C:12]([OH:14])=O)=[CH:5][C:4]=1[C:21]([F:24])([F:23])[F:22])#[N:2].C(Cl)(=O)C(Cl)=O.C[N:32](C=O)C.[NH4+].[OH-]>C(Cl)Cl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:16][C:17]([F:20])([F:19])[F:18])[CH2:10][CH:11]([CH3:15])[C:12]([NH2:32])=[O:14])=[CH:5][C:4]=1[C:21]([F:23])([F:24])[F:22])#[N:2]

参加物

6

反応物 4

HCID 6228Dimethylformamide2 回HCID 14923Ammonium HydroxideHCID 65578Oxalyl chloride2 回HCID 57633744HCID 57633744、化合物

生成物 1

HCID 57633767HCID 57633767、化合物収率 88%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
42 °C

実験手順

To an ice-cold solution of 3-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]-2-methylpropanoic acid (0.050 g, 0.14 mmol) in CH2Cl2 (3 mL), under nitrogen was added oxalyl chloride (0.023 g, 0.18 mmol) and DMF (cat) and the mixture was heated at 42° C. for 30 min. Upon cooling, additional oxalyl chloride (0.014 g, 0.11 mmol) and DMF (cat.) were added and heated for 30 min. Upon cooling, NH4OH (30% aqueous solution, 5 mL) was added and the mixture stirred at rt. After 1 h, the mixture was partitioned between CH2Cl2 and water. The organic phase was washed with 0.1N HCl and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (1-5% MeOH—CH2Cl2 gradient) to give the title compound (0.044 g, 88% yield): 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J=8.6 Hz, 1H), 7.01 (d, J=2.6 Hz, 1H), 6.89 (dd, J=8.6, 2.6 Hz, 1H), 5.70 (bs, NH), 5.54 (bs, NH), 4.22-4.08 (m, 2H), 3.85 (dd, J=15.4, 10.3 Hz, 1H), 3.54 (dd, J=15.4, 3.7 Hz, 1H), 2.80-2.70 (m, 1H), 1.23 (d, J=7.0 Hz, 3H).

後処理

  1. temperatureUpon cooling
  2. temperatureheated for 30 min
  3. temperatureUpon cooling
  4. customthe mixture was partitioned between CH2Cl2 and water
  5. washThe organic phase was washed with 0.1N HCl and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (1-5% MeOH—CH2Cl2 gradient)

出典と根拠

ORDレコード
ord-86cd01b9ece6482ea5036e32d26c4acb
出典データセット
uspto-grants-2010_05
特許番号
US07723385B2

反応ノート

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