Formaldehyde → HCID 69452543, compound

HRID 860170Notes

Reaction equation

HRID 860170 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:10][N:11]1[C:15]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:14][C:13]([CH3:22])=[N:12]1.[C:23](O)(C(F)(F)F)=O.C=O.[BH4-].[Na+].[NH4+].[Cl-]>CCO.Cl>[CH3:10][N:11]1[C:15]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:23][CH2:2][CH:1]([C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)[OH:3])[CH2:18][CH2:17]2)=[CH:14][C:13]([CH3:22])=[N:12]1

Participants

9

Reactant 6

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 7410AcetophenoneHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride2×HCID 82600334HCID 82600334, compound

Product 1

HCID 69452543HCID 69452543, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

A mixture of acetophenone (414 mg, 3.45 mmol), 4-(2,5-dimethyl-2H-pyrazol-3-yl)piperidine.TFA salt (prepared as described for 4-(2-ethyl-5-methyl-2H-pyrazol-3-yl)piperidine in Example 3, Steps 1 and 2) (1.1 g, 3.80 mmol) and paraformaldehyde (120 mg, 4 mmol) in EtOH (2 mL) and conc. HCl (5 μL) was heated at reflux for 14 h and then cooled to RT and concentrated under reduced pressure. The residue was taken up in EtOH (10 mL), NaBH4 (260 mg, 6.9 mmol) added and the mixture stirred at RT for 15 min, then more NaBH4 (260 mg, 6.9 mmol) was added. After stirring for a further 5 min, NH4Cl solution (5 mL) was added and the organic solvents removed under reduced pressure. The aqueous was extracted with CH2Cl2 (3×50 mL). The organic extracts were concentrated under reduced pressure whilst dry loading onto MgSO4 and purified by column chromatography on silica eluting with 8% MeOH/CH2Cl2 to yield the desired alcohol (334 mg, 28%). 1H NMR (CDCl3, 400 MHz) δ 7.43–7.32 (4H, m), 7.29–7.22 (1H, m), 5.81 (1H, s), 4.95 (1H, dd, J=7.0, 4.4 Hz), 3.74 (3H, s), 3.21 (1H, d, J=12.3 Hz), 3.14 (1H, d, J=11.9 Hz), 2.75–2.67 (1H, m), 2.63–2.52 (2H, m), 2.24–2.15 (1H, m), 2.22 (3H, s), 2.06–1.65 (7H, m). MS (ES+) C19H27N3O requires: 313, found: 314 (M+H+, 100%).

Workup

  1. temperatureat reflux for 14 h
  2. concentrationconcentrated under reduced pressure
  3. stirringAfter stirring for a further 5 min
  4. customthe organic solvents removed under reduced pressure
  5. extractionThe aqueous was extracted with CH2Cl2 (3×50 mL)
  6. concentrationThe organic extracts were concentrated under reduced pressure
  7. customwhilst dry loading onto MgSO4
  8. custompurified by column chromatography on silica eluting with 8% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-c6ca9690443a4104b43719eaf8710720
Source dataset
uspto-grants-2006_12
Patent number
US07153868B2

Reaction notes

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