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Hydrochloric Acid → Tapentadol Hydrochloride

HRID 1771015
ノート
印刷プレビュー

反応式

HRID 1771015 の反応式
[H-].[H-].[H-].[H-].[Al+3].[Li+].[CH2:7]([C@@H:9]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=1)[C@@H:10]([CH3:16])[C:11]([N:13]([CH3:15])[CH3:14])=O)[CH3:8].[ClH:24].CO>O1CCCC1>[ClH:24].[CH3:15][N:13]([CH3:14])[CH2:11][C@H:10]([CH3:16])[C@H:9]([C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1)[CH2:7][CH3:8]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 21226445Aluminium lithium hydrideHCID 58555147(alphaR,betaR)-beta-ethyl-3-hydroxy-N,N,alpha-trimethylbenzenepropanamide

生成物 1

HCID 9838021Tapentadol Hydrochloride収率 90%

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒
2 回

実験手順

Lithium aluminum tetrahydride (730 mg, 20 mmol) was suspended in tetrahydrofuran (10 ml), and it was cooled in an ice-water bath, then the solution of product of Example 26 (2 g, 8.5 mmol) in tetrahydrofuran (10 ml) was added dropwise, the reaction was carried out for 2 hours and then quenched by adding 10% NaOH aqueous solution. The reaction solution was then extracted with ethyl acetate for three times, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated to 2 mL, then the concentrated hydrochloric acid (710 μl, 8.5 mmol) was added dropwise therein, and the resulted solution was concentrated and recrystallized with isopropanol-ethyl acetate to obtain the target 1.97 g, yield: 90%. [α]D=+24.3° (c=1.10, CH3OH). 1HNMR (300 MHz, CD3OD): δ 7.2 (1H, t, J=7.9, 15.6), 6.6-6.8 (3H, m), 2.8-2.9 (2H, m), 2.7-2.8 (6H, br s), 2.2-2.3 (1H, m), 2.1-2.2 (1H, m), 1.8-1.9 (1H, m), 1.5-1.6 (1H, m), 1.2 (3H, d, J=6.7), 0.8 (3H, t, J=7.4, 14.4). ESI-MS: 222.4 (M+H).

後処理

  1. temperatureit was cooled in an ice-water bath
  2. customquenched
  3. additionby adding 10% NaOH aqueous solution
  4. extractionThe reaction solution was then extracted with ethyl acetate for three times
  5. washwashed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated to 2 mL
  8. concentrationthe resulted solution was concentrated
  9. customrecrystallized with isopropanol-ethyl acetate
  10. customto obtain the target 1.97 g, yield: 90%

出典と根拠

ORDレコード
ord-67fedeeba6ef4cfb95866b9f324f8e28
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09249084B2

反応ノート

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