Dimethyl Sulfide → 3-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propan-1-amine

HRID 2194926Notes

Reaction equation

HRID 2194926 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:15][C:14]=2[CH3:30])[C:11]#[N:12])[CH:5]=[C:6]([F:8])[CH:7]=1.CSC>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH2:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:15][C:14]=2[CH3:30])[CH2:11][NH2:12])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 674487153-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propanenitrile

Product 1

HCID 584884533-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propan-1-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(3,5-difluorophenyl)-2-[2′-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propanenitrile from step 3 (1 eq.) in THF (0.1M) was added borane-dimethyl sulfide complex (5 eq.). The mixture was refluxed for 5 h without a condensor to release the dimethylsulfide. The final concentration was 0.2M. The mixture was cooled to room temperature, quenched slowly with HCl (1N). The pH was set to 10 using NaOH (1N) and finally the mixture was extracted with CH2Cl2. The organic extract was dried over Na2SO4 filtered and concentrated. Purification by column chromatography on silica gel eluting with CH2Cl2/MeOH(NH3; 2M) 5% afforded the desired compound as a colorless oil. 1H NMR (500 MHz, CD3OD): δ 7.42 (d, 1H), 7.30-7.26 (m, 2H), 7.23-7.20 (m, 2H), 7.12 (d, 1H), 7.04 (s, 1H), 6.76-6.72 (m, 1H), 6.66-6.63 (m, 2H), 3.53-3.50 (m, 1H), 3.25-3.20 (m, 7H), 3.15 (dd, 1H), 2.88 (dd, 1H), 2.65 (d, 1H), 2.64 (d, 1H), 2.12 (s, 3H), 1.70-1.65 (m, 2H).

Workup

  1. temperatureThe mixture was refluxed for 5 h without a condensor
  2. customquenched slowly with HCl (1N)
  3. extractionfinally the mixture was extracted with CH2Cl2
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel eluting with CH2Cl2/MeOH(NH3; 2M) 5%

Sources & evidence

ORD record
ord-7d9f6ef02cba4365adfc558700baadf1
Source dataset
uspto-grants-2012_12
Patent number
US08334308B2

Reaction notes

Loading…