Acetic Acid → (S)-N,N-dimethyl-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-amine

HRID 502765Notes

Reaction equation

HRID 502765 reaction equation
Cl.Cl.[N+:3]([C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[N:16]1[CH2:21][CH2:20][CH2:19][C@H:18](N)[CH2:17]1)([O-:5])=[O:4].C=O.[C:25](O)(=O)C.[C:29]([BH3-])#[N:30].[Na+]>CO>[CH3:25][N:30]([CH3:29])[C@H:18]1[CH2:19][CH2:20][CH2:21][N:16]([C:7]2[CH:8]=[CH:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][C:6]=2[N+:3]([O-:5])=[O:4])[CH2:17]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 16109043(S)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-amine dihydrochloride

Product 1

HCID 16109033(S)-N,N-dimethyl-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a yellow solution of (S)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-amine dihydrochloride (13.39 g, 37 mmol) in 123 mL MeOH under nitrogen at 0° C. was added formaldehyde (37% solution) (14 ml, 185 mmol), Acetic acid (11 ml, 185 mmol), and sodium cyanoborohydride (4.6 g, 74 mmol) in portions over 5 min. The cloudy mixture was warmed to ambient temperature. After 10 min, the reaction became quite hot and was cooled with an ice bath. After 1.5 h, the reaction was complete by LCMS. The solvent was removed in vacuo, and the flask cooled to 0° C. Water was added, and the mixture was basified with 1N NaOH, and 6N NaOH. The mixture was extracted with 1×200 mL EtOAc, 1×100 mL EtOAc, and the combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo to give (S)-N,N-dimethyl-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-amine as an orange oil. MS m/z=318 [M+H]+. Calc'd for C14H18F3N3O2: 317.

Workup

  1. temperaturewas cooled with an ice bath
  2. waitAfter 1.5 h
  3. customThe solvent was removed in vacuo
  4. temperaturethe flask cooled to 0° C
  5. additionWater was added
  6. extractionThe mixture was extracted with 1×200 mL EtOAc, 1×100 mL EtOAc
  7. dry with materialthe combined organics were dried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6cce2630f3424a09b584eb231ef77fdf
Source dataset
uspto-grants-2010_08
Patent number
US07776869B2

Reaction notes

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