Acetaldehyde → tert-Butyl-4-{ethyl[3-(methoxycarbonyl)-2-methyl-5-(trifluoromethyl)phenyl]amino}piperidine-1-carboxylate

HRID 2208664Notes

Reaction equation

HRID 2208664 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:29])=[C:7]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)=[O:4].[CH:30](=O)[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)=O>[C:25]([O:24][C:22]([N:19]1[CH2:18][CH2:17][CH:16]([N:15]([CH2:30][CH3:31])[C:7]2[CH:8]=[C:9]([C:11]([F:13])([F:14])[F:12])[CH:10]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[C:6]=2[CH3:29])[CH2:21][CH2:20]1)=[O:23])([CH3:26])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86719530Tert-butyl 4-{[3-(methoxycarbonyl)-2-methyl-5-(trifluoromethyl)phenyl]amino}piperidine-1-carboxylate

Product 1

HCID 86719531tert-Butyl-4-{ethyl[3-(methoxycarbonyl)-2-methyl-5-(trifluoromethyl)phenyl]amino}piperidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of tert-butyl 4-{[3-(methoxycarbonyl)-2-methyl-5-(trifluoromethyl)phenyl]amino}piperidine-1-carboxylate (10.6 g, 25.4 mmol) in CH2Cl2 (200 mL) and AcOH (10 mL) was added acetaldehyde (2.80 g, 63.5 mmol) and sodium triacetoxyborohydride (13.4 g, 63.5 mmol). The reaction mixture was stirred at 23° C. for 24 hours. Then saturated NaHCO3 was added and the mixture was separated. The aqueous layer was extracted with CH2Cl2 (3×50 mL) and the combined organic layer was concentrated in vacuo. The residue was purified by silica gel column chromatography (SiO2 Heptane/EtOAc=5/1) to give the titled compound as oil (4.50 g, 40% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.82 (br. s., 1H), 7.45 (d, J=1.6 Hz, 1H), 3.96-4.18 (m, 2H), 3.92 (s, 3H), 3.08 (q, J=7.0 Hz, 2H), 2.89 (tt, J=11.0, 3.7 Hz, 1H), 2.69 (m, 2H), 2.55 (s, 3H), 1.73 (m, 2H), 1.49-1.56 (m, 2H), 1.45 (s, 9H), 0.86 (t, J=7.0 Hz, 3H); MS (ES) [M+Na] 467.0.

Workup

  1. customthe mixture was separated
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
  3. concentrationthe combined organic layer was concentrated in vacuo
  4. customThe residue was purified by silica gel column chromatography (SiO2 Heptane/EtOAc=5/1)

Sources & evidence

ORD record
ord-d7dab9fd8e4b46b8a22a314e897edbbc
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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