Hydrochloric Acid → 2-methyl-N-(thietan-3-yl)-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzamide

HRID 1770643ノート

反応式

HRID 1770643 の反応式
[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[OH-].[Na+].C(N(CC)CC)C.[S:50]1[CH2:53][CH:52]([NH2:54])[CH2:51]1>ClCCl>[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:18])([F:19])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:54][CH:52]1[CH2:53][S:50][CH2:51]1)=[O:6]

参加物

9

反応物 7

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 14594132Thietan-3-amineHCID 867270182-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoic acid

生成物 1

HCID 867270192-methyl-N-(thietan-3-yl)-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
30 °C

実験手順

To a solution of 2-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoic acid (28.72 mmol, 13 g) in dichloromethane (100 mL) and N,N-dimethylformamide (0.2867 mmol, 0.0210 g) was added oxalyl chloride (4.836 g) dropwise at room temperature and under argon (the liberated hydrochloric acid gas was scrubbed with a sodium hydroxide 0.5N solution). The mixture was stirred at room temperature for 1 h and at 30° C. for 20 min until the gas evolution ceased. The reaction mixture was concentrated to dryness and redissolved in dichloromethane (100 mL), triethylamine (71.81 mmol, 7.340 g) was added at 0-5° C. under argon followed by dropwise addition of thietan-3-amine (28.72 mmol, 2.561 g). The mixture was allowed to warm to room temperature and stirred for 16 h. The mixture was extracted with aqueous hydrochloric acid (0.5N), water, brine, dried over MgSO4, filtered and evaporated affording the crude product. Purification over silica gel (eluent: CH2Cl2/EtOAc) yielded the title compound. LCMS (Method GR) RT 1.25 min, [M+H]+ 523/525; 1H-NMR (CDCl3, 400 MHz): 2.45 (s, 3H), 3.35 (m, 2H), 3.50 (m, 2H), 3.60 (d, 1H), 74.10 (d, 1H), 5.40 (q, 1H), 6.20 (d, NH), 7.40 (s, 1H), 7.51 (d, 1H), 7.40 (s, 1H), 7.50 (s, 2H), 7.65 (s, 2H). 19F-NMR (CDCl3, 376 MHz): −79.43.

後処理

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutionredissolved in dichloromethane (100 mL)
  3. temperatureto warm to room temperature
  4. stirringstirred for 16 h
  5. extractionThe mixture was extracted with aqueous hydrochloric acid (0.5N), water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customaffording the crude product
  10. customPurification over silica gel (eluent: CH2Cl2/EtOAc)

出典と根拠

ORDレコード
ord-b937993aad594f32a756884483cb982a
出典データセット
uspto-grants-2016_02
特許番号
US09247740B2

反応ノート

読み込み中…