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

HRID 2210297ノート

反応式

HRID 2210297 の反応式
C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.Cl.Cl.[OH:17][CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH:19]1[N:24]1[CH2:29][CH2:28][C:27]2([C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32][CH2:31][CH2:30]2)[CH2:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+].[I:45][C:46]1[CH:53]=[CH:52][CH:51]=[CH:50][C:47]=1[CH2:48]Cl>ClCCl.O.CN(C=O)C>[I:45][C:46]1[CH:53]=[CH:52][CH:51]=[CH:50][C:47]=1[CH2:48][N:21]1[CH2:22][CH2:23][CH:18]([OH:17])[CH:19]([N:24]2[CH2:29][CH2:28][C:27]3([C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][CH2:31][CH2:30]3)[CH2:26][CH2:25]2)[CH2:20]1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 1010641-(Chloromethyl)-2-iodobenzeneHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 19426302HCID 19426302、化合物

生成物 1

HCID 156376351'-(1-(2-Iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4-dihydrospiro[naphthalene-1(2H),4'-piperidine]

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of the dihydrochloride of 21c (250 mg, 0.67 mmol), DMF (10 mL), potassium carbonate (463 mg, 3.35 mmol) and 2-iodobenzyl chloride (1.00 mmol, 254 mg) was stirred at room temperature for 18 h. Water (25 mL) and dichloromethane (2×25 mL) were added and the organic layer was extracted, washed with brine (25 mL), dried (Na2SO4) and concentrated. The crude product was purified by chromatography (silica gel, hexanes/ethyl acetate, 50/50) to afford 13c as a yellow oil. The latter was converted to the corresponding hydrochloride in satd HCl/ether and recrystallized twice from 50% i-PrOH-hexanes to yield 0.20 g (33%) of 13c; mp 258.8° C. 1H NMR (CDCl3)δ1.50-2.21 (2 m, 8, 2 N-CH2 --CH2), 2.45-2.57 (m, 2H, Ar-CH2CH2, J=10.2 Hz), 2.60- 2.76 (m, 2, CH2CHOH), 2.84 (m, 4, Ar-CH2 --CH2 --CH2), 2.88-3.00 (t, 2, CH2 --CH2CHOH, J=11.2 Hz), 3.09-3.13 (d, 2, N-CH2 --CHN, J=8.7 Hz), 3.50-3.64 (m, 3, Ar-CH2N+CH-N), 3.85 (s, 1, CHOH), 4.67 (s, 1, OH), 6.96-7.49 (m, 8 H, arom.), 7.83-7.87 (d, 1 H, arom., J=6.8 Hz).

後処理

  1. extractionthe organic layer was extracted
  2. washwashed with brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by chromatography (silica gel, hexanes/ethyl acetate, 50/50)

出典と根拠

ORDレコード
ord-e3badc8a889646e8ae8cd53b47ea06ec
出典データセット
uspto-grants-1995_10
特許番号
US05457207

反応ノート

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