Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Hydrochloric Acid | HCID 313 | — |
| Reactant | Formaldehyde | HCID 712 | — |
| Reactant | Water | HCID 962 | — |
| Reactant | Sodium Bicarbonate | HCID 516892 | — |
| Reactant | Sodium triacetoxyborohydride | HCID 5049666 | — |
| Reactant | HCID 86657773 | HCID 86657773 | — |
| Catalyst | Acetic Acid | HCID 176 | — |
| Solvent | Diethyl Ether | HCID 3283 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Solvent | Water ethylacetate | HCID 22728543 | — |
| Product | HCID 86657771 | HCID 86657771 | 164.6% |
Reaction Steps
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).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09045461B2 |
|---|
| Source dataset | uspto-grants-2015_06 |
|---|
| ORD ID | ord-c1d116b4701243a09be80cb5f0c2aaef |
|---|
| Source note | uspto-grants-2015_06 |
|---|