Acetone → Methyl 3-{ethyl[1-(propan-2-yl)piperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoate

HRID 2208667Notes

Reaction equation

HRID 2208667 reaction equation
OC(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].[CH3:32][C:33]([CH3:35])=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]([CH:33]([CH3:35])[CH3:32])[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 180AcetoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 131735971Methyl 3-[ethyl(piperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoate TFA salt

Product 1

HCID 70873916Methyl 3-{ethyl[1-(propan-2-yl)piperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoateYield 17%

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, 1.30 g, 3.36 mmol) in CH2Cl2 (20 mL) and AcOH (5 mL) was added acetone (590 mg, 10.1 mmol) and sodium triacetoxyborohydride (1.80 g, 8.40 mmol). The reaction mixture was stirred at 23° C. for 6 days and then saturated NaHCO3 was added and the mixture was separated. The aqueous layer was extracted with CH2Cl2 (3×30 mL) and the combined organic layer was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH—SiO2 heptane/ethylacetate=5/1) to give the titled compound as oil (220 mg, 17% yield). 1HNMR (400 MHz, CDCl3) δppm; 7.79 (br. s., 1H), 7.44 (d, J=1.6 Hz, 1H), 3.91 (s, 3H), 3.10 (q, J=7.0 Hz, 2H), 2.86 (m, 2H), 2.61-2.75 (m, 2H), 2.53 (s, 3H), 2.06 (m, 2H), 1.70-1.80 (m, 2H), 1.58-1.69 (m, 2H), 1.00 (s×2, 6H), 0.84 (t, J=7.0 Hz, 3H); MS (ES) [M+H] 387.2.

Workup

  1. customthe mixture was separated
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×30 mL)
  3. concentrationthe combined organic layer was concentrated in vacuo
  4. customThe residue was purified by silica gel column chromatography (NH—SiO2 heptane/ethylacetate=5/1)

Sources & evidence

ORD record
ord-1c025a185fc54d8ea96727e0ef761240
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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