Benzaldehyde → (+/-)-6-[4-(1-Benzyl-piperidin-3-yl)-phenoxy]-nicotinamide

HRID 228202Notes

Reaction equation

HRID 228202 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[CH:23]=[CH:22][C:11]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:10][CH:9]=2)[CH2:3]1.[CH:24](=O)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH4-].[Na+]>C(#N)C.CO>[CH2:24]([N:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[CH:9]=[CH:10][C:11]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:22][CH:23]=2)[CH2:3]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 240Benzaldehyde2×HCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 68747046(+/-)-6-(4-Piperidin-3-yl-phenoxy)-nicotinamide hydrochloride2×

Product 1

HCID 59730236(+/-)-6-[4-(1-Benzyl-piperidin-3-yl)-phenoxy]-nicotinamideYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

Combine 6-(4-Piperidin-3-yl-phenoxy)-nicotinamide (free base of compound of example 322) (0.0298 g, 0.101 mmol), benzaldehyde (0.0108 mL, 0.106 mmol), and sodium triacetoxyborohydride (0.0310 mg, 0.146 mmol) in acetonitrile (2.0 mL). Add methanol (0.5 mL) to dissolve insoluble starting material. Add benzaldehyde (0.0200 mL, 0.197 mmol) after 15 min. then stir for 4 h. Add sodium borohydride (0.0083 g, 0.219 mmol) and stir for 10 min., concentrate, and purify by silica gel chromatography (30:1 ethyl acetate:hexanes → 20:1 ethyl acetate:methanol) to provide 0.0223 g (57%) of the title compound as a white solid: mass spectrum (electrospray): m/z=388.2 (M+1); 1H NMR (CDCl3): 8.56 (d, 1H, J=2.4 Hz), 8.14 (dd, 1H, J=2.4, 8.8 Hz), 7.33-7.29 (m, 4H), 7.27-7.22 (m, 3H), 5.84 (s br, 2H), 3.57 (m, 2H), 3.06-2.83 (m, 3H), 2.10-1.90 (m, 4H), 1.80-1.70 (m, 2H), 1.50-1.37 (m, 1H).

Workup

  1. concentrationconcentrate
  2. custompurify by silica gel chromatography (30:1 ethyl acetate:hexanes → 20:1 ethyl acetate:methanol)

Sources & evidence

ORD record
ord-e88f133a14274a2abe2fa54cffe25b28
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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