Sodium Iodide → N-(3-(1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamide

HRID 1269150Notes

Reaction equation

HRID 1269150 reaction equation
Cl[CH2:2][CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[CH3:12][CH:13]([CH3:29])[C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:18]=1)=[O:15].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>O.CN(C=O)C>[OH:5][C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][CH2:2][N:26]1[CH2:27][CH2:28][CH:23]([C:19]2[CH:18]=[C:17]([NH:16][C:14](=[O:15])[CH:13]([CH3:12])[CH3:29])[CH:22]=[CH:21][CH:20]=2)[CH2:24][CH2:25]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 642409(1R)-3-chloro-1-phenylpropan-1-olHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamide

Product 1

HCID 10199805N-(3-(1-[(3R)-3-hydroxy-3-phenylpropyl]-4-piperidinyl}phenyl)-2-methylpropanamideYield 94.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Into a 25-mL RB-flask was added (R)-(+)-3-chloro-1-phenyl-1-propanol (0.545 g, 3.19 mmol, 99% ee, Aldrich Chemical Co.), 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (0.748 g, 3.04 mmol), potassium carbonate (0.420 g, 3.04 mmol), sodium iodide (0.684 g, 4.56 mmol) and DMF (6.0 mL) at room temperature. After stirring at 100° C. for 3 hrs, TLC showed that the reaction was complete. The reaction mixture was cooled to room temperature and poured into water (50 mL) and the aqueous layer was extracted with methylene chloride (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (1:1=hexane: ethyl acetate with 1% isopropylamine) to afford the desired product (1.09 g, 94% yield) as a light-yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 7.46–7.35 (m, 6H), 7.27 (m, 2H), 6.98 (apparent d, 1H, J=7.6 Hz), 5.02 (apparent dd, 1H, J=4.4, 8.1 Hz), 3.18 (apparent dd, 2H, J=2.5, 12.5 Hz), 2.74 (m, 2H), 2.50 (m, 2H), 2.30–2.10 (m, 6H), 1.80 (m, 2H), 1.25 (d, 6H, J=7.1 Hz); ESMS m/e: 381.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe aqueous layer was extracted with methylene chloride (3×20 mL)
  3. washThe combined organic extracts were washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (1:1=hexane: ethyl acetate with 1% isopropylamine)

Sources & evidence

ORD record
ord-22c8edff69a64d469ad101988e5b6a54
Source dataset
uspto-grants-2007_04
Patent number
US07199135B2

Reaction notes

Loading…