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Hydrochloric Acid → Tapentadol Hydrochloride

HRID 1771015
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HRID 1771015 반응식
[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]
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참가 물질

6

반응물 4

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

생성물 1

HCID 9838021Tapentadol Hydrochloride수율 90%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매
2회

실험 절차

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).

후처리

  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%

출처 및 근거

ORD 기록
ord-67fedeeba6ef4cfb95866b9f324f8e28
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09249084B2

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