Methyl iodide → 4-((alpha-r)-alpha-((2s,5r)-2,5-Dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-n,n-diethylbenzamide

HRID 1038637노트

반응식

HRID 1038637 반응식
[H-].[Na+].[CH3:3][C@H:4]1[CH2:9][N:8]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C@H:7]([CH3:18])[CH2:6][N:5]1[C@H:19]([C:27]1[CH:39]=[CH:38][C:30]([C:31]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[O:32])=[CH:29][CH:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=1.[CH3:40]I>CCCCC.O1CCCC1>[CH3:3][C@H:4]1[CH2:9][N:8]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)[C@H:7]([CH3:18])[CH2:6][N:5]1[C@H:19]([C:27]1[CH:28]=[CH:29][C:30]([C:31]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[O:32])=[CH:38][CH:39]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:40])[CH:21]=1

참가 물질

6

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 103008024-((alpha-r)-alpha-((2s,5r)-2,5-Dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-hydroxybenzyl)-n,n-diethylbenzamide2회

생성물 1

HCID 101862094-((alpha-r)-alpha-((2s,5r)-2,5-Dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-n,n-diethylbenzamide

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8028Tetrahydrofuran용매

실험 절차

Sodium hydride (60% dispersion in oil, 400 mg (240 mg NaH, 10 mmol)) was washed with pentane (2×7 mL), and tetrahydrofuran (10 mL) was added. The product from Example 11, 4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (1.007 g, 2.0 mmol) was dissolved in the stirred suspension, and when effervescence had subsided, methyl iodide (249 δL, 568 mg, 4 mmol) was added. The reaction mixture was sealed under nitrogen and stirred for 6 h at ambient temperature. The reaction mixture was evaporated to dryness, and the residue was partitioned between ethyl acetate (15 mL) and water (5 mL). The organic layer was separated, the aqueous portion extracted with ethyl acetate (2×10 mL) and the combined organic extracts were dried over anhydrous sodium sulfate. The organic solution was evaporated to a pale yellow gum, which on trituration and sonication with pentane yielded 4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide as a flocculent white solid (0.798 g, 77% after drying at room temperature and 5 mm Hg). Calc. for C32H40FN3O2 0.25 H2O: C, 73.60; H, 7.82; N, 8.05; F, 3.64. Found C, 73.58; H, 7.70; N, 8.04; F, 3.84% 1H NMR (CDCl3, 300 MHz); δ 1.09 (d, J=6.2 Hz, 6H, superimposed on br m, 3H); 1.21 (br m, 3H); 1.99 (m, 2H); 2.57 (br m, 2H); 2.66 (m, 3H); 3.15 (d, J=13.3 Hz, 1H); 3.27 (br m, 2H); 3.54 (br m, 2H); 3.78 (s, 3H); 3.84 (d, J=13 Hz, 1H); 5.10 (s, 1H); 6.76 (s, 1H); 6.70 (d, J=8.1 Hz, 2H); 6.96 (t, J=8.2 Hz, 2H); 7.26 (m, 5H); 7.46 (d, J=7.8 Hz, 2H).

후처리

  1. additionwas added
  2. customThe reaction mixture was sealed under nitrogen
  3. customThe reaction mixture was evaporated to dryness
  4. customthe residue was partitioned between ethyl acetate (15 mL) and water (5 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous portion extracted with ethyl acetate (2×10 mL)
  7. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  8. customThe organic solution was evaporated to a pale yellow gum, which on trituration and sonication with pentane
  9. customyielded
  10. dry with material4-((alpha-R)-alpha-((2S,5R)-2,5-dimethyl-4-(4-fluorobenzyl)-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide as a flocculent white solid (0.798 g, 77% after drying at room temperature and 5 mm Hg)

출처 및 근거

ORD 기록
ord-35baf205efc54ddba567cf8b899b2596
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551998B2

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