Oxalyl chloride → 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-(5-trifluoromethyl-pyridin-2-yl)-propionamide

HRID 1355180ノート

反応式

HRID 1355180 の反応式
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[F:34][C:35]([F:44])([F:43])[C:36]1[CH:37]=[CH:38][C:39]([NH2:42])=[N:40][CH:41]=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:42][C:39]2[CH:38]=[CH:37][C:36]([C:35]([F:43])([F:34])[F:44])=[CH:41][N:40]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

9

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 12069486(2R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid

生成物 1

HCID 599740093-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-(5-trifluoromethyl-pyridin-2-yl)-propionamide収率 26%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
25 °C

実験手順

A solution of 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionic acid (prepared as in Example 54A, 200 mg, 0.69 mmol) in methylene chloride (10 mL) and one drop of N,N-dimethylformamide was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.42 mL, 0.84 mmol). Gas evolution began immediately. The reaction mixture was allowed to warm slowly to 25° C. where it was stirred for 30 min. After this time, the reaction mixture was treated with a solution of N,N-diisopropylethylamine (0.24 mL, 1.39 mmol) and 5-trifluoromethyl-2-aminopyridine (150 mg, 0.905 mmol) in tetrahydrofuran (4 mL) in one portion. The resulting reaction mixture was stirred for 16 h at 25° C. After such time, the reaction was diluted with water (15 mL) and was extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 90/10 hexanes/ethyl acetate) afforded the 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-(5-trifluoromethyl-pyridin-2-yl)-propionamide (77 mg, 26%) as a white solid: mp 113.8–117.5° C.; EI-HRMS m/e calcd for C20H19C12F3N2O (M+) 430.0826, found 430.0835.

後処理

  1. customThe resulting reaction mixture
  2. stirringwas stirred for 16 h at 25° C
  3. extractionwas extracted with methylene chloride (3×15 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1c3e1015e8b34873a9fe1918536158c4
出典データセット
uspto-grants-2007_05
特許番号
US07223868B2

反応ノート

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