Hydrochloric Acid → HCID 86657771, compound

HRID 1971882Notes

Reaction equation

HRID 1971882 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@@H:29]3[CH2:33][NH:32][CH2:31][C@H:30]3[CH2:34][OH:35])[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=O.O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].Cl>ClCCl.C(O)(=O)C.O.C(OCC)(=O)C.CCOCC>[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@@H:29]3[CH2:33][N:32]([CH3:39])[CH2:31][C@H:30]3[CH2:34][OH:35])[N:20]=[N:21][C:22]=2[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:15][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86657773HCID 86657773, compound

Product 1

HCID 86657771HCID 86657771, compoundYield 164.6%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 22728543Water ethylacetateSolvent

Procedure

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).

Workup

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
  4. customto give a solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-3a5594bdb19544699bbca03d944e32a4
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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