2-Butene, 1-bromo-3-methyl- → (S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

HRID 990332ノート

反応式

HRID 990332 の反応式
[ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH2:20])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.Br[CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42]>C1COCC1>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH:20][CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:7][CH:8]=1

参加物

5

反応物 3

HCID 700922-Butene, 1-bromo-3-methyl-HCID 81531DiisopropylethylamineHCID 86758543(S)-2-Amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

生成物 1

HCID 9912978(S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride収率 36%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of (S)-2-amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride (0.36 g, 0.88 mmol, Example 7) in THF (15 mL) were added, in succession, N,N-diisopropylethylamine (0.30 mL, 1.7 mmol) and 1-bromo-3-methyl-2-butene (0.10 mL, 0.87 mmol) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was stirred for 12 hours at that temperature, 16 hours at 50° C., cooled to ambient temperature, and concentrated in vacuo. The desired product was purified by flash chromatography (50% EtOAc in hexanes) and was dissolved in 10 mL of ethyl ether. To this solution was added saturated HCl solution in ethyl ether until no more white precipitate formed. Filtration and drying overnight under vacuum afforded 0.14 g (36%) of the titled compound as a yellow foam; mp 58-72° C. APCI-MS m/z 443.3 (MH+).

後処理

  1. customThe resulting reaction mixture
  2. temperaturecooled to ambient temperature
  3. concentrationconcentrated in vacuo
  4. customThe desired product was purified by flash chromatography (50% EtOAc in hexanes)
  5. dissolutionwas dissolved in 10 mL of ethyl ether
  6. additionTo this solution was added saturated HCl solution in ethyl ether until no more white precipitate
  7. customformed
  8. filtrationFiltration
  9. customdrying overnight under vacuum

出典と根拠

ORDレコード
ord-e93e117dde3242fc8cdb6042b746e2df
出典データセット
uspto-grants-2002_10
特許番号
US06458781B1

反応ノート

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