Hydrochloric Acid → HCID 86657780, compound

HRID 2168635Notes

Reaction equation

HRID 2168635 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:12]=[N:11][C:10]([O:13][CH2:14][C@H:15]2[CH2:20][CH2:19][NH:18][CH2:17][C@H:16]2[OH:21])=[CH:9][C:8]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:24][CH:23]=1)[CH2:4][CH2:5][CH3:6].C=O.O.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(O)(=O)C.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:12]=[N:11][C:10]([O:13][CH2:14][C@H:15]2[CH2:20][CH2:19][N:18]([CH3:38])[CH2:17][C@H:16]2[OH:21])=[CH:9][C:8]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:24][CH:23]=1)[CH2:4][CH2:5][CH3:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 86657781HCID 86657781, compound

Product 1

HCID 86657780HCID 86657780, compoundYield 96.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (±)-cis-4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-piperidin-3-ol dihydrochloride (Example 35, ˜0.2 mmol) 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, worked up and the solvent was removed in vacuo. The residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, condensed, triturated with hexanes to provide title compound (51 mg). LCMS: m/z 455 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.48 (1H, s), 7.39-7.43 (2H, m), 7.08-7.12 (2H, m), 4.52-4.59 (1H, m), 4.39-4.48 (2H, m), 4.27 (1H, bs), 3.38-3.54 (2H, m), 3.02-3.26 (4H, m), 2.85 (3H, s), 2.25-2.37 (1H, m), 1.78-2.07 (6H, m), 1.20-1.43 (10H, 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 colorless sticky solid, which
  5. customcondensed
  6. customtriturated with hexanes

Sources & evidence

ORD record
ord-10c4459ce5b74850bbe97f4ab7d3ff04
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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