반응 #489060

반응 방정식

sodium triacetoxyborohydride

HCl

pyridazine dihydrochloride

(±)-trans-4-(4-benzyloxy-phenyl)-3-butyl-6-(4-methoxymethyl-pyrrolidin-3-ylmethoxy)-pyridazine di hydrochloride

formaldehyde

water

→

title compound

수율 153.9%

(±)-trans-4-(4-Benzyloxy-phenyl)-3-butyl-6-(4-methoxymethyl-1-methyl-pyrrolidin-3-ylmethoxy)-pyridazine dihydrochloride

수율 153.9%

용매

DCM

ether

dichloromethane

반응 조건

후처리

1. 1
   농축then concentrated
2. 2
   workup.ADDITIONThe mixture was then diluted with water/EtOAc
3. 3
   건조dried over Na2SO4
4. 4
   기타The solvent was removed in vacuo
5. 5
   기타the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
6. 6
   기타to give a solid, which
7. 7
   workup.WAITkept at room temperature for 10 min
8. 8
   기타condensed
9. 9
   기타triturated with hexanes

실험 절차

To a solution of the above pyridazine dihydrochloride (0.5 mmol, 267 mg) in dichloromethane (2.0 mL) was added formaldehyde solution in water (37%, 10 mmol, 1.0 mL), and 2 drops of acetic acid. Then sodium triacetoxyborohydride (10 mmol, 2.12 g) was added. The mixture was stirred at room temperature for 0.5 hour then concentrated. The mixture was then diluted with water/EtOAc, and neutralized with NaHCO3 powder. The organic layers were combined and dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to give a solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (211 mg). LCMS: m/z 477 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.83 and 7.93 (1H, s), 7.45-7.55 (4H, m), 7.36-7.40 (2H, m), 7.31-7.35 (1H, m), 7.20-7.24 (2H, m), 5.20 (2H, s), 4.59-4.63 (2H, m), 3.63-3.95 (4H, m), 3.44 (3H, s), 2.58-3.23 (9H, m), 1.44-1.53 (2H, m), 1.25-1.33 (2H, m), 0.81 (3H, t).

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