Acetic Acid → 1-Methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine

HRID 2247173Notes

Reaction equation

HRID 2247173 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)[O:7][CH2:8][CH:9]1[CH2:13][CH2:12][CH2:11][NH:10]1)([O-:3])=[O:2].C=O.[BH3-][C:24]#N.[Na+].CC(O)=O>CC#N>[CH3:24][N:10]1[CH2:11][CH2:12][CH2:13][CH:9]1[CH2:8][O:7][C:6]1[CH:14]=[C:15]([C:17]([F:20])([F:18])[F:19])[CH:16]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 219594182-(3-Nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine

Product 1

HCID 219594761-Methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-(3-Nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine (6 mmol) was dissolved in CH3CN (20 ml) and formaldehyde (2.4 ml, 37% aqueous) was added. NaBH3CN (607 mg) was added, an exotherm was observed. The pH is monitored every 15 min and adjusted to ˜7 with AcOH. After 45 min, the mixture was concentrated in vacuo and the residue is dissolved in EtOAc, washed with 6N NaOH, 1N NaOH, and 2N HCl (3×). The acid washings were combined, adjusted to ˜pH 10 with solid Na2CO3 and extracted with EtOAc (2×). The EtOAc fractions were combined, dried with Na2SO4, and purified with flash chromatography (SiO2, 95:5:0.5 CH2Cl2:MeOH:NH4OH) to afford 1-methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionthe residue is dissolved in EtOAc
  3. washwashed with 6N NaOH, 1N NaOH, and 2N HCl (3×)
  4. extractionextracted with EtOAc (2×)
  5. dry with materialdried with Na2SO4
  6. custompurified with flash chromatography (SiO2, 95:5:0.5 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-f9f80188ab2d43aab2cb689ce03177b5
Source dataset
uspto-grants-2010_03
Patent number
US07687643B2

Reaction notes

Loading…