(2S)-2,5-Dihydro-2-isopropyl-3,6-dimethoxypyrazine → (2R,5S)-2,5-dihydro-3,6-dimethoxy-2-(2'-fluoro-4'-(trifluoromethyl)benzyl)-5-isopropylpyrazine

HRID 1272366노트

반응식

HRID 1272366 반응식
[CH3:1][O:2][C:3]1[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])CCC.[F:19][C:20]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=1[CH2:22]Br>O1CCCC1>[CH3:10][O:9][C:6]1[C@@H:7]([CH2:22][C:21]2[CH:24]=[CH:25][C:26]([C:28]([F:29])([F:31])[F:30])=[CH:27][C:20]=2[F:19])[N:8]=[C:3]([O:2][CH3:1])[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=1

참가 물질

5

반응물 3

HCID 736065(2S)-2,5-Dihydro-2-isopropyl-3,6-dimethoxypyrazineHCID 27375702-Fluoro-4-(trifluoromethyl)benzyl bromideHCID 178418339Butyllithium

생성물 1

HCID 20628238(2R,5S)-2,5-dihydro-3,6-dimethoxy-2-(2'-fluoro-4'-(trifluoromethyl)benzyl)-5-isopropylpyrazine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 3.32 g (18 mmol) of commercially available (2S)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at −70° C. was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4-trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0–5% ethyl acetate in hexanes) afforded 5.5 g of the title compound. 1H NMR (500 MHz, CDCl3) δ 7.33–7.25 (m, 3H), 4.35–4.31 (m, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.60 (t, 1H, J=3.4 Hz), 3.33 (dd, 1H, J=4.6, 13.5 Hz), 3.03 (dd, 1H, J=7, 13.5 Hz), 2.25–2.15 (m, 1H), 1.0 (d, 3H, J=7 Hz), 0.66 (d, 3H, J=7 Hz).

후처리

  1. stirringstirring
  2. waitwas continued for 3 h
  3. temperaturebefore warming
  4. customthe reaction to ambient temperature
  5. customThe reaction was quenched with water
  6. concentrationconcentrated in vacuo
  7. extractionextracted with ethyl acetate
  8. washThe combined organic phase was washed with brine
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography (silica gel, 0–5% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-99bd99fa30394f948563cd3ba2d04b20
출처 데이터셋
uspto-grants-2007_04
특허 번호
US07208498B2

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