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Potassium Carbonate → (S)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate

HRID 42997
ノート
印刷プレビュー

反応式

HRID 42997 の反応式
[CH2:1]([O:8][C:9](=[O:22])[NH:10][C@@H:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20]O)[CH:17]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[F:33][C:34]([F:43])([F:42])[C:35]1[C:39]([CH2:40][OH:41])=[CH:38][NH:37][N:36]=1>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:8][C:9](=[O:22])[NH:10][C@@H:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][N:37]3[CH:38]=[C:39]([CH2:40][OH:41])[C:35]([C:34]([F:33])([F:42])[F:43])=[N:36]3)[CH:17]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 70224068(S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamateHCID 178519885HCID 178519885、化合物

生成物 1

HCID 68364703(S)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate収率 84.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

(S)-benzyl-5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate (7.13 mmol, 2.12 g) was dissolved in DCM (20 mL), thionyl chloride (14.26 mmol, 1.040 mL, 1.696 g) added and the resultant solution stirred at room temperature for 45 min. The sample was concentrated and azeotroped with dichloromethane (×4). Potassium carbonate (21.39 mmol, 2.96 g) was added followed by DMF (20 mL) and (3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (7.13 mmol, 1.184 g) and the mixture heated to 60° C. for 1 h. The mixture was concentrated and partitioned between ethylacetate/water. The aqueous layer was twice extracted with ethylacetate and combined organics dried, filtered and concentrated to give a yellow oil which was purified on silica eluting with 0-1% MeOH/DCM to give (S)-benzyl-5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate as a light coloured oil (2.67 g, 84%). 1H NMR (400 MHz, CDCl3) δ 1.83 (t, 1H) 2.79 (m, 2H) 3.27 (m, 2H) 4.51 (bs, 1H) 4.63 (d, 2H) 4.98 (bs, 1H) 5.08 (bs, 2H) 5.24 (s, 2H) 7.05-7.11 (m, 2H) 7.18 (m, 1H) 7.26-7.39 (m, 6H).

後処理

  1. concentrationThe sample was concentrated
  2. customazeotroped with dichloromethane (×4)
  3. concentrationThe mixture was concentrated
  4. custompartitioned between ethylacetate/water
  5. extractionThe aqueous layer was twice extracted with ethylacetate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil which
  9. customwas purified on silica eluting with 0-1% MeOH/DCM

出典と根拠

ORDレコード
ord-1e44daefd0074a3da9d471c2e5e783f7
出典データセット
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08536214B2

反応ノート

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