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

HRID 1909610Notes

Reaction equation

[CH:1]1[CH:2]=[CH:3][C:4]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=2)=[CH:5][CH:6]=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]([CH2:7][C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=2)=[CH:13][CH:12]=1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 4-hydroxydiphenylmethane (0.77 g, 4.18 mmol) in anhydrous DMF (22.5 mL) at 0° C. was added a 60% dispersion of NaH in mineral oil (0.23 g, 5.75 mmol) portionwise over 5 min. The resulting slurry was stirred at 0° C. for 45 minutes before a solution of tosylate from step 1 (1.50 g, 4.22 mmol) in DMF (11 mL) was added dropwise over 5 min. The subsequent mixture was stirred at 60° C. overnight. The reaction mixture was poured over ice and then concentrated under reduced pressure. The crude residue was extracted into ethyl acetate and sequentially washed with water, saturated aq. NaHCO3, water and brine. The combined organic layer was dried anhydrous Na2SO4, filtered and concentrated in vacuo to afford the title compound (1.8 g, >100%) as a tan oil;

Workup

additionwas added dropwise over 5 min
additionThe reaction mixture was poured over ice
concentrationconcentrated under reduced pressure
extractionThe crude residue was extracted into ethyl acetate
washsequentially washed with water, saturated aq. NaHCO3, water and brine
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-f944c85d246b45d088140f9a53db0e5d
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598359B2

Reaction notes

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