Water → (R*)-3-[1-((S)-7-Fluoro-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-3-yl]phenol

HRID 2407266Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11]OS(C)(=O)=O)[O:7][C:6]=2[CH:17]=1.Br.[NH:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]2[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=2)[CH2:20]1.C([O-])(O)=O.[Na+].O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11][N:19]3[CH2:24][CH2:23][CH2:22][C@H:21]([C:25]4[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=4)[CH2:20]3)[O:7][C:6]=2[CH:17]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of methanesulfonic acid (R)-(7-fluoro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl ester (51 mg, 0.19 mmol), (R*)-3-(piperidin-3-yl)phenol HBr (50 mg, 0.19 mmol) and NaHCO3 (33 mg, 0.39 mmol) in DMF (3.5 ml) was heated at 120° C. for 1.5 h. Water (10 ml) was added to the cooled mixture, which was then extracted with EtOAc (3×10 ml). The combined organic layers were washed several times with water and finally twice with brine. Drying (Na2SO4), filtering and evaporation of the solvent gave the crude product, which was recrystallised from EtOH to afford 24 mg of the title compound as a white solid.

Workup

extractionwas then extracted with EtOAc (3×10 ml)
washThe combined organic layers were washed several times with water
dry with materialDrying (Na2SO4)
filtrationfiltering
customevaporation of the solvent
customgave the crude product, which
customwas recrystallised from EtOH

Sources & evidence

ORD record: ord-c3bc7df9f6d341a3b95d6804356abbba
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809536B2

Reaction notes

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