Hydrochloric Acid → (1R)-N-[3,5-bis(trifluoromethyl)phenyl]-1,8,8-trimethyl-2,4-dioxobicyclo [3.2.1]octane-3-carboxamide

HRID 349778ノート

反応式

HRID 349778 の反応式
[CH3:1][C@:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[CH2:4][C:3]2=[O:13].C(N(CC)CC)C.[F:21][C:22]([F:37])([F:36])[C:23]1[CH:24]=[C:25]([N:33]=[C:34]=[O:35])[CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1.Cl>CN(C)C1C=CN=CC=1.ClCCl>[F:21][C:22]([F:36])([F:37])[C:23]1[CH:24]=[C:25]([NH:33][C:34]([CH:4]2[C:5](=[O:12])[CH:6]3[C:9]([CH3:10])([CH3:11])[C@@:2]([CH3:1])([CH2:8][CH2:7]3)[C:3]2=[O:13])=[O:35])[CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 58805524(1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

生成物 1

HCID 11582906(1R)-N-[3,5-bis(trifluoromethyl)phenyl]-1,8,8-trimethyl-2,4-dioxobicyclo [3.2.1]octane-3-carboxamide収率 51%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
30 °C

実験手順

To an ice-cooled solution of (1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.36 g, 2.0 mmole), triethylamine (0.20 g, 2.0 mmole) and 4-(dimethylamino)pyridine (0.24 g, 2.0 mmole) in dry dichloromethane (25 mL) was added a solution of 3,5-bis-(trifluoromethyl)phenyl isocyanate (0.51 g, 2.0 mmole) in dry dichloromethane (5 mL). The resulting mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature, and then was heated at 30° C. for 7 hours. The reaction mixture was treated with 2N aqueous HCl and the layers separated. The acidic aqueous layer was extracted with two additional portions of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to give a yellow oil, which was purified by chromatography on silica gel (10% ethyl acetate/hexane) to yield a yellow oil, which was crystallized from 95% ethanol to yield the title compound as a yellow solid (0.44 g, 51% yield), mp=68–71° C.; MS (−) ESI m/z=434 (M−H)−; [α]D25=+22.8° (c=1, EtOH).

後処理

  1. customcame up to room temperature
  2. customthe layers separated
  3. extractionThe acidic aqueous layer was extracted with two additional portions of dichloromethane
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated on a rotary evaporator
  6. customto give a yellow oil, which
  7. customwas purified by chromatography on silica gel (10% ethyl acetate/hexane)
  8. customto yield a yellow oil, which
  9. customwas crystallized from 95% ethanol

出典と根拠

ORDレコード
ord-7174745bd65a474983d3f9f8da136831
出典データセット
uspto-grants-2007_02
特許番号
US07179943B2

反応ノート

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