Water → (R)-3-chloro-N-[1-(4-chlorophenyl)ethyl]-3-methyl-1-(trifluoromethyl)cyclobutanecarboxamide

HRID 1270809ノート

反応式

HRID 1270809 の反応式
[Cl:1][C:2]1([CH3:13])[CH2:5][C:4]([C:9]([F:12])([F:11])[F:10])([C:6]([OH:8])=O)[CH2:3]1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C@@H:27]([CH3:29])[NH2:28])=[CH:23][CH:22]=1.O>S(Cl)(Cl)=O.O1CCOCC1.O>[Cl:1][C:2]1([CH3:13])[CH2:3][C:4]([C:9]([F:12])([F:11])[F:10])([C:6]([NH:28][C@@H:27]([C:24]2[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=2)[CH3:29])=[O:8])[CH2:5]1

参加物

7

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 1715226(1R)-1-(4-chlorophenyl)ethan-1-amineHCID 109219311-(Trifluoromethyl)-3-chloro-3-methylcyclobutane-1-carboxylic acid

生成物 1

HCID 23550325(R)-3-chloro-N-[1-(4-chlorophenyl)ethyl]-3-methyl-1-(trifluoromethyl)cyclobutanecarboxamide

試薬・触媒・溶媒 2

HCID 24386Thionyl Chloride溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
0 °C

実験手順

A solution of 0.240 g (1.11 mmol) of 3-chloro-3-methyl-1-(trifluoromethyl)cyclobutane carboxylic acid (prepared according to the method described by H. K. Hall, Jr., E. P. Blanchard Jr. and E. L. Martin in Macromolecules 4(2) 142–146 (1971)) in 5 mL thionyl chloride was heated at reflux for 1 h. Solvent was removed in vacuo. The residue was added to a solution of 0.176 g (1.66 mmol) sodium carbonate and 0.172 g (1.11 mmol) (R)-4-chloro-α-methylbenzenemethanamine in 6 mL of 1:1 dioxane-water, pre-cooled to 0° C. After stirring at room temperature overnight, the mixture was poured into 50 mL water and extracted two times with 50 mL ethyl acetate (EtOAc). Drying (magnesium sulfate) and removal of the solvent gave an oil which was chromatographed on silica gel, eluting with 25% hexane-dichloromethane, to afford 43 mg of the cis isomer of the title compound: mp 129–130° C., 1H NMR (CDCl3) δ 1.49 (d, 3H), 1.69 (s, 3H), 2.86–2.95 (m, 2H), 2.98–3.05 (m, 2H), 5.05–5.12 (q, 1H), 5.86 (s, 1H), 7.20 (d, 2H), 7.32 (d, 2H), and 77 mg of the trans isomer of the title compound: mp 145–146 C, 1H NMR (CDCl3) 1.54 (d, 3H), 1.74 (s, 3H), 2.79–2.86 (m, 2H), 3.13 (d, 2H), 5.14 (q, 1H), 5.85 (s, 1H), 7.23 (d, 2H), 7.31 (d, 2H).

後処理

  1. temperatureat reflux for 1 h
  2. customSolvent was removed in vacuo
  3. extractionextracted two times with 50 mL ethyl acetate (EtOAc)
  4. customDrying
  5. custom(magnesium sulfate) and removal of the solvent
  6. customgave an oil which
  7. customwas chromatographed on silica gel
  8. washeluting with 25% hexane-dichloromethane

出典と根拠

ORDレコード
ord-6ca15b6ec0fb4fecb98f93d88784b446
出典データセット
uspto-grants-2007_04
特許番号
US07202404B2

反応ノート

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