Nitromethane → 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester

HRID 589626

反応式

HRID 589626 の反応式
[N+:1]([CH3:4])([O-:3])=[O:2].[C:5]([O:9][C:10](=[O:34])[C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:32])/[CH:18]=[C:19](\[C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)/[C:20]([F:23])([F:22])[F:21])=[CH:13][C:12]=1[CH3:33])([CH3:8])([CH3:7])[CH3:6]>O>[C:5]([O:9][C:10](=[O:34])[C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:32])[CH2:18][C@@:19]([C:24]2[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)([CH2:4][N+:1]([O-:3])=[O:2])[C:20]([F:22])([F:21])[F:23])=[CH:13][C:12]=1[CH3:33])([CH3:8])([CH3:7])[CH3:6]

参加物

4

反応物 2

HCID 6375NitromethaneHCID 866959924-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester

生成物 1

HCID 547615654-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

Alternatively, to a solution of 3-[3,5-bis(trifluoromethyl)anilino]-4-[[(S)-(6-methoxy-4-quinolyl)-[(1S,2S,5S)-5-vinylquinuclidin-2-yl]methyl]amino]cyclobut-3-ene-1,2-dione (13 mg, prepared according to the literature: Org. Lett., 2010, 12 (23), 5450-5453) and nitromethane (0.6 ml) under argon, was added 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (100 mg). The solution was heated for 5 days at 50° C. then more catalyst (15 mg) was added. The reaction was heated again for 3 days at 50° C. then allowed to stand at room temperature for 15 days. Water was then added and the resulting mixture was extracted with dichloromethane and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester (26 mg). Chiral HPLC analysis (Chiralpack IA, Heptane:2-propanol=90:10, 1 ml/min, retention time 6.13 minutes (major enantiomer), 7.29 minutes (minor enantiomer) indicated that the reaction proceeded with 61% enantioselectivity in favor of the R enantiomer.

後処理

  1. temperatureThe reaction was heated again for 3 days at 50° C.
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. dry with materialthe combined organic fractions were dried over sodium sulfate
  4. customThe crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-580cc2c3d43a428cbe5984ad6ae2fd41
出典データセット
uspto-grants-2016_01
特許番号
US09233920B2

関連ノート

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