Hydrochloric Acid → HCID 6918426, compound

HRID 1955219Notes

Reaction equation

HRID 1955219 reaction equation
[ClH:1].C([O:9][C:10]1[CH:33]=[CH:32][C:13]([O:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][C:20]([OH:31])([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)[CH2:19][CH2:18]2)=[CH:12][CH:11]=1)C1C=CC=CC=1.C(OC1C=CC(OCCBr)=CC=1)C1C=CC=CC=1.Cl.CC1C=CC(CC2(O)CCNCC2)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>C(#N)C.CO.CCOCC>[ClH:1].[OH:9][C:10]1[CH:11]=[CH:12][C:13]([O:14][CH2:15][CH2:16][N:17]2[CH2:18][CH2:19][C:20]([OH:31])([CH2:23][C:24]3[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=3)[CH2:21][CH2:22]2)=[CH:32][CH:33]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 107570881-(Benzyloxy)-4-(2-bromoethoxy)benzeneHCID 226283764-[(4-Methylphenyl)methyl]piperidin-4-ol hydrochlorideHCID 69704311193357-90-3

Product 1

HCID 6918426HCID 6918426, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

1-[2-(4-Benzyloxyphenoxy)ethyl]-4-hydroxy-4-(4-methylbenzyl)piperidine hydrochloride. A mixture of 2-(4-benzyloxyphenoxy)ethyl bromide (368 mg, 1.2 mmol), 4-(4-methylbenzyl)-4-hydroxypiperidine hydrochloride (290 mg, 1.2 mmol), potassium carbonate (414 mg, 3 mmol) in 30 mL of acetonitrile was allowed to reflux for 12 h. The inorganic salt was removed through a short column of silica gel and washed with ethyl acetate (3×25 mL). The combined flitrate was evaporated in vacuo to give a crude mixture, which was purified by flash chromatography (5% methanol in ethyl acetate), giving a pale yellow oil, which was disolved into methanol (10 mL), to which was added 4 mL of 1 M HCl in methanol. The resulting solution was allowed to stir at rt for 10 min, and methanol was evaporated in vacuo to give a residue, to which 50 mL of ether was added. The resulting mixture was stirred overnight. A white solid was collected by filtration and dried in vacuo, giving 420 mg (75%) of the title product: mp 179-181° C. 1H NMR (CDCl3) 1.605 (s, 2 H), 1.725 (d, J=14.1 Hz, 2 H), 2.332 (s, 3 H), 2.453 (m, 2 H), 2.809 (s, 2 H), 3.221 (m, 2 H), 3.361 (s, 1 H), 3.464 (d, J=8.4 Hz, 2 H), 4.488 (s, 2 H), 5.005 (s, 2 H), 6.820 (d, J=9.0 Hz, 2 H), 6.904 (d, J=9.0 Hz, 2 H), 7.077 (d, J=7.5 Hz, 2 H), 7.166 (d, J=7.5 Hz, 2 H), 7.376 (m, 5 H), 12.4 (bs, 1 H).

Workup

  1. temperatureto reflux for 12 h
  2. customThe inorganic salt was removed through a short column of silica gel
  3. washwashed with ethyl acetate (3×25 mL)
  4. customThe combined flitrate was evaporated in vacuo
  5. customto give a crude mixture, which
  6. customwas purified by flash chromatography (5% methanol in ethyl acetate)
  7. customgiving a pale yellow oil, which
  8. custommethanol was evaporated in vacuo
  9. customto give a residue
  10. stirringThe resulting mixture was stirred overnight
  11. filtrationA white solid was collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-ac3df140f4c8451da714b58d29d0238a
Source dataset
uspto-grants-2000_09
Patent number
US06124323

Reaction notes

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