Tetrahydrofuran → HCID 67784806, compound

HRID 2210416Notes

Reaction equation

HRID 2210416 reaction equation
C([Li])CCC.[N:6]1([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[Cl:22][C:23]1[CH:41]=[CH:40][C:26]([CH2:27][CH:28]2[C:32](=O)[C:31]3[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:30]=3[O:29]2)=[CH:25][CH:24]=1.C1C[O:45]CC1>>[Cl:22][C:23]1[CH:41]=[CH:40][C:26]([CH2:27][C:28]2([OH:45])[CH:32]([C:18]3[CH:19]=[CH:20][C:15]([O:14][CH2:13][CH2:12][N:6]4[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]4)=[CH:16][CH:17]=3)[C:31]3[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:30]=3[O:29]2)=[CH:25][CH:24]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8671951-[2-(4-Bromophenoxy)ethyl]piperidineHCID 15169092HCID 15169092, compoundHCID 178418339Butyllithium

Product 1

HCID 67784806HCID 67784806, compound

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (5.27 ml, 7.80 mM) in THF was added dropwise to a solution of 4-[2-piperidinoethoxy]phenyl bromide (1.45 g, 7.80 mmol) in THF (5 ml) at -78° C. After stirring for 30 minutes at -78° C., 2-(p-chlorobenzyl)-6-methoxy-3(2H)- benzofuranone (1.50 g, 5.20 mmol) in THF was added dropwise to the mixture at -78° C. The reaction mixture was stirred at -78° C. for 1 hour. It was warmed to room temperature. After stirring for 18 hours, it was quenched with saturated ammonium chloride and THF was evaporated off. The residue was dissolved in ethyl acetate (30 ml), washed with sodium chloride (2×20 ml), dried (anhydrous magnesium sulphate) and the solvent evaporated off to yield an oil which was purified by flash chromatography (eluent, dichloromethane:hexane: triethylamine=1:1:0.2), yielding a light brown oil of the tertiary alcohol, 2-(p-chlorobenzyl)-3-[p-(2-piperidinoethoxy)phenyl] -6-methoxybenzofuranol (Rf =0.23) which gave a characteristic reddish stain with ammonium molybdate-ceric sulphate in 2M sulphuric acid spray. A solution of methanol (0.40 ml) saturated with dry hydrogen chloride gas was added to the tertiary alcohol dissolved in sodium-dried ether (40 ml). The reaction mixture was stirred at room temperature for 1/2 hour. A white precipitate was formed which was filtered and recrystallised from ethanol to give the hydrochloride salt of the title compound as a white crystalline solid. Yield (74%); m.p. 133°-136° C.; 1H-NMR (CDCl3 3) δ 1:58-3.03 (bm, 10H, N(CH2CH2)2CH2), 3.42 (t, 2H, J 6.0 Hz, OCH2CH2N), 3.85 (s, 3H, OCH3), 4.10 (s, 2H, CH2 at C-2), 4.44 (t, 2H, J 6.0 Hz, OCH2CH2N), 6.81-7.44 (m, 11H, ArH); m/z (%) 477 (M+ -HCl, 8), 475 (M+ -HCl, 3), 364 (13), 98 (100). (Found: C, 64.89, H, 6.20, N, 2.49, Cl, 13.38. C29H3oO3ClN.HCl.3/2H2O required C, 64.56, H, 6.35, N, 2.60, Cl, 13.14).

Workup

  1. stirringThe reaction mixture was stirred at -78° C. for 1 hour
  2. temperatureIt was warmed to room temperature
  3. stirringAfter stirring for 18 hours
  4. customit was quenched with saturated ammonium chloride and THF
  5. customwas evaporated off
  6. dissolutionThe residue was dissolved in ethyl acetate (30 ml)
  7. washwashed with sodium chloride (2×20 ml)
  8. dry with materialdried (anhydrous magnesium sulphate)
  9. customthe solvent evaporated off
  10. customto yield an oil which
  11. customwas purified by flash chromatography (eluent, dichloromethane:hexane: triethylamine=1:1:0.2)

Sources & evidence

ORD record
ord-726b7986ef4d4e2d9ba04bc5e3a0c385
Source dataset
uspto-grants-1995_10
Patent number
US05459139

Reaction notes

Loading…