Methanol → 3-[4-(Imidazol-1-yl)phenoxy]-1-[(4-methoxynaphth-1-yl)methyl]piperidine

HRID 1270464Notes

Reaction equation

HRID 1270464 reaction equation
[N:1]1([C:6]2[CH:18]=[CH:17][C:9]([O:10][CH:11]3[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.CO.[CH3:21][O:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH:33]=O)=[CH:25][CH:24]=1>C(Cl)Cl>[N:1]1([C:6]2[CH:18]=[CH:17][C:9]([O:10][CH:11]3[CH2:16][CH2:15][CH2:14][N:13]([CH2:33][C:26]4[C:27]5[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:23]([O:22][CH3:21])=[CH:24][CH:25]=4)[CH2:12]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 852174-Methoxy-1-naphthaldehydeHCID 222600603-[4-(Imidazol-1-yl)phenoxy]piperidine

Product 1

HCID 222600553-[4-(Imidazol-1-yl)phenoxy]-1-[(4-methoxynaphth-1-yl)methyl]piperidineYield 10.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-[4-(imidazol-1-yl)phenoxy]piperidine (308 mg, 1.26 mmol), methanol (6.0 mL) was added 4-methoxy-1-naphthaldehyde (1.25 eq, 298 mg), followed by borane pyridine complex (0.196 mL, 1.25 eq.). The resulting mixture was stirred overnight. The methanol was evaporated, and the residue diluted with ethyl acetate, washed with water and brine. Evaporation of the solvent in vacuo gave a crude product. Flash column chromatography on silical gel with 1–2% methanol in methylene chloride afforded 3-[4-(imidazol-1-yl)phenoxy]-1-[(4-methoxynaphth-1-yl)methyl]piperidine (54 mg), 1H NMR(CDCl3) 8.30 (m, 2), 7.70 (s, 1), 7.50 (m, 2), 7.30 (s, 1), 7.20 (m, 4), 6.90 (m, 2), 6.70 (d, 2), 4.30 (m, 1), 4.00 (s, 3), 3.90 (AB q , 2), 3.10 (m, 1), 2.80 (m, 1), 2.10–2.30 (m, 3), 1.80 (m, 1), 1.40–1.70 (m, 2) ppm.

Workup

  1. customThe methanol was evaporated
  2. additionthe residue diluted with ethyl acetate
  3. washwashed with water and brine
  4. customEvaporation of the solvent in vacuo
  5. customgave a crude product

Sources & evidence

ORD record
ord-9d25b3e234464a259b48fb1cde04b7ba
Source dataset
uspto-grants-2007_04
Patent number
US07202263B2

Reaction notes

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