Trifluoroacetic acid → 1-Benzyl-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine

HRID 1508313Notes

Reaction equation

HRID 1508313 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]([F:13])([F:12])[F:11])=[CH2:9])[CH:5]=[C:4]([Cl:14])[CH:3]=1.[CH2:15]([N:22]([CH2:28]OC)[CH2:23][Si](C)(C)C)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:15]([N:22]1[CH2:28][CH2:9][C:8]([C:6]2[CH:5]=[C:4]([Cl:14])[CH:3]=[C:2]([Cl:1])[CH:7]=2)([C:10]([F:11])([F:13])[F:12])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 231598231,3-Dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene

Product 1

HCID 582188831-Benzyl-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidineYield 48.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (10 g, 41.49 mmol) in DCM (150 mL) was added benzyl-methoxymethyl-trimethylsilanylmethyl-amine (Preparation 29, 39.33 g, 165.97 mmol) at room temperature. Resulting reaction mixture was cooled to 0° C. and TFA (0.32 mL, 0.41) was added slowly and stirred at room temperature for 5 hours. After complete consumption of starting material, reaction mixture was basified by aqueous Na2CO3 and extracted with DCM (3×100 mL). Combined organic layer was dried over Na2SO4, and concentrated under vacuum to afford brown oil (9.5 g, crude). Crude compound was purified by column chromatography using 100-200 mesh silica gel. Desired product was eluted in 2% ethyl acetate in hexane to afford product as brown solid (7.5 g, 48.29%). 1H-NMR (400 MHz, CDCl3) δ: 2.28-2.35 (m, 1H), 2.53-2.60 (m, 1H), 2.69-2.81 (m, 2H), 3.03-3.11 (m, 2H), 3.66 (s, 2H), 7.26-7.35 (m, 8H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. extractionextracted with DCM (3×100 mL)
  5. dry with materialCombined organic layer was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto afford brown oil (9.5 g, crude)
  8. customCrude compound was purified by column chromatography
  9. washDesired product was eluted in 2% ethyl acetate in hexane

Sources & evidence

ORD record
ord-382c00e9e41c401a9c53758e55410691
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

Loading…