Formaldehyde → Methyl 3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoate

HRID 2208666Notes

Reaction equation

HRID 2208666 reaction equation
O[C:2](C(F)(F)F)=O.[CH2:8]([N:10]([CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:11]1[C:12]([CH3:25])=[C:13]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[C:14]([O:16][CH3:17])=[O:15])[CH3:9].C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)=O>[CH2:8]([N:10]([CH:26]1[CH2:31][CH2:30][N:29]([CH3:2])[CH2:28][CH2:27]1)[C:11]1[C:12]([CH3:25])=[C:13]([CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1)[C:14]([O:16][CH3:17])=[O:15])[CH3:9]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 131735971Methyl 3-[ethyl(piperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoate TFA salt

Product 1

HCID 70873889Methyl 3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoateYield 28%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of methyl 3-[ethyl(piperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoate TFA salt (crude material, 5.30 g, 12.0 mmol) in CH2Cl2 (150 mL) and AcOH (10 mL) was added formaldehyde (15 mL, 44% aqueous solution) and sodium triacetoxyborohydride (6.40 g, 30.0 mmol). The reaction mixture was stirred at 23° C. for 2.5 days. Then saturated NaHCO3 was added and the mixture was separated. The aqueous layer was extracted with CH2Cl2 (3×50 mL) and the combined organic layers were concentrated in vacuo. The residue was purified by silica gel column chromatography (NH—SiO2 heptane/EtOAc=2/1) to give the titled compound as oil (1.20 cg, 28% yield). 1H-NMR (400 cMHz, CDCl3) δppm; 7.81 (br. s., 1H), 7.45 (d, J=2.0 Hz, 1H), 3.92 (s, 3H), 3.10 (q, J=7.0 Hz, 2H), 2.83 (m, 2H), 2.66-2.77 (m, 1H), 2.54 (s, 3H), 2.24 (s, 3H), 1.84-1.94 (m, 2H), 1.63-1.78 (m, 4H), 0.86 (t, J=7.0 Hz, 3H); MS (ES) [M+H] 359.1.

Workup

  1. customthe mixture was separated
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
  3. concentrationthe combined organic layers were concentrated in vacuo
  4. customThe residue was purified by silica gel column chromatography (NH—SiO2 heptane/EtOAc=2/1)

Sources & evidence

ORD record
ord-744425ac79054cfea46b3646c830c789
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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