반응 #489058

반응 방정식

sodium triacetoxyborohydride

HCl

NaHCO3

(±)-trans-{4-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-pyrrolidin-3-yl}-methanol dihydrochloride

formaldehyde

water

→

title compound

수율 164.6%

(±)-trans-{4-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-1-methyl-pyrrolidin-3-yl}-methanol dihydrochloride

수율 164.6%

용매

ether

water ethyl acetate

DCM

dichloromethane

반응 조건

후처리

1. 1
   기타condensed
2. 2
   기타The solvent was removed in vacuo
3. 3
   기타the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
4. 4
   기타to give a solid, which
5. 5
   workup.WAITkept at room temperature for 10 min
6. 6
   기타condensed
7. 7
   기타triturated with hexanes

실험 절차

To a solution of (±)-trans-{4-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-pyrrolidin-3-yl}-methanol dihydrochloride (0.2 mmol, 104 mg) in dichloromethane (2.0 mL) was added formaldehyde solution in water (37%, 2.0 mmol, 0.2 mL), and 1 drop of acetic acid. Then sodium triacetoxyborohydride (2.0 mmol, 424 mg) was added. The mixture was stirred at room temperature for 0.5 hour then condensed, diluted with water/ethyl acetate, and neutralized with NaHCO3 powder. 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 yield the title compound (88 mg). LCMS: m/z 464 [M+2]. 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), 2.58-3.3 (9H, m), 1.44-1.53 (2H, m), 1.25-1.33 (2H, m), 0.81 (3H, t).

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