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

HRID 2210297Notes

Reaction equation

HRID 2210297 reaction equation
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

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 1010641-(Chloromethyl)-2-iodobenzeneHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 19426302HCID 19426302, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e3badc8a889646e8ae8cd53b47ea06ec
Source dataset
uspto-grants-1995_10
Patent number
US05457207

Reaction notes

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