Triethylamine → 1'-(1-(3-Iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4-dihydrospiro[naphthalene-1(2H),4'-piperidine]

HRID 742555노트

반응식

HRID 742555 반응식
Cl.Cl.[OH:3][CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[N:10]1[CH2:15][CH2:14][C:13]2([C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][CH2:17][CH2:16]2)[CH2:12][CH2:11]1.[I:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[CH2:29]Br.C(N(CC)CC)C>CCO>[I:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[CH2:29][N:7]1[CH2:8][CH2:9][CH:4]([OH:3])[CH:5]([N:10]2[CH2:15][CH2:14][C:13]3([C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16]3)[CH2:12][CH2:11]2)[CH2:6]1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27593613-Iodobenzyl bromideHCID 19426302HCID 19426302, 화합물

생성물 1

HCID 156376381'-(1-(3-Iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4-dihydrospiro[naphthalene-1(2H),4'-piperidine]

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A mixture of 21c and 22c derived from a mixture of 19c and 20c as described above (676 mg, 1.81 mmol), 3-iodobenzylbromide (2.17 mmol, 645 mg), and triethylamine (10 mL) in absolute EtOH (20 mL) was refluxed for 18 h. Volatiles were removed under reduced pressure and the red residue was treated with water. After extraction in dichloromethane (3×30 mL), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give a dark red semi-solid residue. Chromatographic purification (silica gel, 50% ethyl acetate-hexanes) afforded 276 mg (30%) of the crude product as a yellow oil. The two regioisomers were separated by HPLC (Silica gel, Hexane/Isopropanol/Triethylamine: 98/2/0.02) and 13d was obtained as a white crystalline solid (166 mg, 18%). Only a trace of the other isomer was recovered. The hydrochloride of 13d was prepared in said methanolic saturated HCl and subsequently recrystallized from 50% i-PrOH-hexanes to provide a white powder; mp 245° C. 1H NMR ((CDCl3) δ1.59-2.06 (m, 8, 2 N--C H2 --C H2), 2.41-2.48 (m, 2, Ar--C H2 --CH2), 2.52-2.62 (m, 2, C H2 --CHOH), 2.75-2.78 (m, 4, Ar--CH2 --C H2 --C H2), 2.83-2.92 (m, 2, C H2 --CH2 --CHOH), 3.01-3.06 (d, 2, N--C H2 --CHN, J=10.0 Hz), 3.38-3.56 (m, 3, Ar--CH2 --N+CH--N), 3.85 (s, 1, C H--OH), 7.02-7.31 (m, 5, arom.), 7.44-7.48 (d, 1, arom., J=7.8 Hz), 7.58-7.62 (d, 1, arom., J=7.9 Hz), 7.68 (s, 1, arom.).

후처리

  1. temperaturewas refluxed for 18 h
  2. customVolatiles were removed under reduced pressure
  3. additionthe red residue was treated with water
  4. extractionAfter extraction in dichloromethane (3×30 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give a dark red semi-solid residue
  9. customChromatographic purification (silica gel, 50% ethyl acetate-hexanes)
  10. customafforded 276 mg (30%) of the crude product as a yellow oil
  11. customThe two regioisomers were separated by HPLC (Silica gel, Hexane/Isopropanol/Triethylamine: 98/2/0.02)

출처 및 근거

ORD 기록
ord-bceadd6c59f94d94ae223b04faaea25c
출처 데이터셋
uspto-grants-1996_09
특허 번호
US05554752

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