Sodium triacetoxyborohydride → HCID 58438346, compound

HRID 1971890Notes

Reaction equation

HRID 1971890 reaction equation
Cl.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.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[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]([CH3:36])[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

4

Reactant 2

HCID 5049666Sodium triacetoxyborohydrideHCID 67373517HCID 67373517, compound

Product 1

HCID 58438346HCID 58438346, 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 reaction
  2. custommay be quenched with saturated NaHCO3
  3. customthe layers may be separated
  4. customThe organic layer may be dried
  5. customthe solvent may be removed under reduced pressure
  6. customThe crude product may be purified by flash chromatography

Sources & evidence

ORD record
ord-2857a7fef98541c696a3687f905b8a73
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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