Formaldehyde → HCID 86657807, compound

HRID 1971967Notes

Reaction equation

HRID 1971967 reaction equation
[CH2:1]([C:5]1[N:10]=[N:9][C:8]([O:11][CH2:12][C@H:13]2[C@H:18]([OH:19])[CH2:17][CH2:16][NH:15][CH2:14]2)=[CH:7][C:6]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH3:4].C=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:1]([C:5]1[N:10]=[N:9][C:8]([O:11][CH2:12][C@H:13]2[C@H:18]([OH:19])[CH2:17][CH2:16][N:15]([CH3:35])[CH2:14]2)=[CH:7][C:6]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86657806HCID 86657806, compound

Product 1

HCID 86657807HCID 86657807, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (±)-trans-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-piperidin-4-ol (0.117 mmol, 0.06 g) in DCM (1 mL) was added formaldehyde solution (1 mL) followed by sodium triacetoxyborohydride (0.3 g) and continued stirring the reaction mixture for 3 h at room temperature. The reaction mixture was diluted with DCM (10 mL), washed the organic layer with water, dried the organic layer, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography by eluting with DCM (200 mL) followed 10% methanolic solution of ammonia (2 M solution of NH3 in methanol) in DCM to provide (±)-trans-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-1-methyl-piperidin-4-ol which was treated with 4 N HCl in dioxane. The volatiles were removed under reduced pressure, and the salt was washed with anhydrous ether and dried under high vacuum to provide the title compound (0.058 g). LCMS: m/z 455 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.81 (1H, s), 7.47 (2H, d), 7.13 (2H, d), 4.6-4.76 (2H, m), 4.42-4.48 (1H, m), 3.52-3.85 (3H, m), 3.12-3.22 (4H, m), 2.92 (3H, s), 2.21-2.36 (2H, m), 1.84-2.04 (4H, m), 1.23-1.64 (11H, m), 0.82 (3H, t).

Workup

  1. washwashed the organic layer with water
  2. customdried the organic layer
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash silica gel column chromatography
  6. washby eluting with DCM (200 mL)

Sources & evidence

ORD record
ord-6b816651c2e84995b388bf266c0a64bb
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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