Hydrochloric Acid → HCID 67372249, compound

HRID 401885Notes

Reaction equation

HRID 401885 reaction equation
[ClH:1].Cl.[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:18]=[C:19]([O:27][CH2:28][C:29]3([OH:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[N:20]=[N:21][C:22]=2[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[CH2:37](OCC)C>C(Cl)Cl>[ClH:1].[ClH:1].[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:18]=[C:19]([O:27][CH2:28][C:29]3([OH:35])[CH2:34][CH2:33][N:32]([CH3:37])[CH2:31][CH2:30]3)[N:20]=[N:21][C:22]=2[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 67373517HCID 67373517, compound

Product 1

HCID 67372249HCID 67372249, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 4-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-piperidin-4-ol dihydrochloride (0.1 mmol) aqueous formaldehyde (37%, 0.3 mmol) and molecular sieves in anhydrous DCM may be stirred for 20 minutes. To this suspension at room temperature may be added sodium triacetoxyborohydride (0.3 mmol). The reaction mixture may be monitored by LCMS until the reaction is complete. The reaction may be quenched with saturated NaHCO3 and the layers may be separated. The organic layer may be dried and the solvent may be removed under reduced pressure. The crude product may be purified by flash chromatography using with 1-5% (2N ammonia in MeOH) in DCM to give 4-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-1-methyl-piperidin-4-ol. The neutral amine may be treated with 2N HCl in diethyl ether and DCM. The volatiles may be removed under reduced pressure and the salt triturated with diethyl ether and filtered to provide the title compound. LCMS: m/z 463 [M+1]. 1H NMR (400 MHz, CDCl3) δ 7.32-7.49 (5H, m), 7.19-7.25 (2H, m), 7.02-7.09 (2H, m), 6.78 (1H, bs), 5.12 (2H, s), 4.58-4.83 (1H, m), 4.32 (2H, s), 2.54-2.69 (3H, m), 2.40-2.51 (2H, m), 2.27-2.36 (3H, m), 1.71-1.83 (2H, m), 1.59-1.70 (2H, m), 1.18-1.51 (5H, m), 0.81 (3H, t).

Workup

  1. customThe volatiles may be removed under reduced pressure
  2. customthe salt triturated with diethyl ether
  3. filtrationfiltered

Sources & evidence

ORD record
ord-4383ff0097ea49269640bd9a2453ac23
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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