4-Benzylphenol → (R)-2-(4-Benzyl-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 749928Notes

Reaction equation

HRID 749928 reaction equation
[CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:17]([O:21][C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@@H:25]1[CH2:29]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:17]([O:21][C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@@H:25]1[CH2:29][O:14][C:11]1[CH:10]=[CH:9][C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][CH:12]=1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 75634-BenzylphenolHCID 24758Sodium hydrideHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 44819341(R)-2-(4-Benzyl-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-benzylphenol (103 mg, 0.56 mmol) in DMF (1 mL) was added 95% NaH (19 mg, 0.75 mmol) at 0° C., and the resulting mixture was stirred at 0° C. for 10 min. A solution of the tosylate (200 mg, 0.56 mmol) from Step 1 in DMF (2 mL) was added to the reaction mixture dropwise over 5 min., and the reaction was heated at 95° C. for 10 h. The mixture was concentrated and water was added, and extracted with EtOAc. The organic layer was washed with saturated aq. NaHCO3 followed by water and brine. Organic layer was dried over anhy. Na2SO4 and the solvent was removed in vacuo to obtain the crude product, which was purified by silica gel flash chromatography to obtain the title product (150 mg, 73%) as a solid: MS; m/z 368 (M+H); 1H NMR (400 MHz, CDCl3); δ 1.46 (m, 9H), 1.84-2.03 (m, 4H), 3.39 (m, 2H), 3.73-3.93 (m, 3H), 4.10 (m, 2H), 6.84 (m, 2H), 7.08 (m, 2H), 7.17 (m, 2H), 7.26 (m, 3H): HPLC (UV), 99.8%.

Workup

  1. temperaturethe reaction was heated at 95° C. for 10 h
  2. concentrationThe mixture was concentrated
  3. additionwater was added
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with saturated aq. NaHCO3
  6. customOrganic layer was dried over anhy
  7. customNa2SO4 and the solvent was removed in vacuo
  8. customto obtain the crude product, which
  9. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-77d405b5c3504c1d968ef46f69b2f5cb
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

Loading…