Hydrochloric Acid → HCID 86657780, compound

HRID 1971913Notes

Reaction equation

HRID 1971913 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-736638c8ed2d42ba84df41256a9f41a5
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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