Aluminum(III) Chloride → 4H-1-Benzopyran-4-one, 6-fluoro-3-(3-fluorophenyl)-2-[(1R)-1-hydroxyethyl]-

HRID 626296Notes

Reaction equation

HRID 626296 reaction equation
C([O:8][C@@H:9]([C:11]1[O:12][C:13]2[C:18]([C:19](=[O:28])[C:20]=1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)=[CH:17][C:16]([F:29])=[CH:15][CH:14]=2)[CH3:10])C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[F:29][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[O:12][C:11]([C@H:9]([OH:8])[CH3:10])=[C:20]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)[C:19]2=[O:28]

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 117867472(R)-2-(1-(benzyloxy)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one

Product 1

HCID 718162794H-1-Benzopyran-4-one, 6-fluoro-3-(3-fluorophenyl)-2-[(1R)-1-hydroxyethyl]-Yield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-2-(1-(benzyloxy)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one (10.5 g, 26.69 mmol) in Dichloromethane (110 ml) cooled to 0° C., anhydrous Aluminium chloride (5.35 g, 40.03 mmol) was added portion wise and stirred for 1 h and then at RT for 2 h. The reaction mixture was quenched with dilute aq. HCl (10 ml), extracted with Dichloromethane (2×50 ml). The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with ethyl acetate:petroleum ether to afford the title compound as off-white solid (6.5 g, 81%). 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.86 (dd, J=8.3, 3.0 Hz, 1H), 7.56 (dd, J=9.2, 4.2 Hz, 1H), 7.45 (m, 2H), 7.12-6.99 (m, 3H), 4.76 (q, J=6.6 Hz, 1H), 1.55 (d, J=6.6 Hz, 3H). Mass: 303.2 (M++1). Purity: 99.78%. [α]25D 0.287 (c=1, CHCl3). Enantiomeric excess: 97.74%, enriched in the late eluting isomer (retention time: 10.93 min.) as determined by HPLC on a chiralpak AD-H column.

Workup

  1. waitat RT for 2 h
  2. customThe reaction mixture was quenched with dilute aq. HCl (10 ml)
  3. extractionextracted with Dichloromethane (2×50 ml)
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography with ethyl acetate

Sources & evidence

ORD record
ord-43e921719ab0413895201e2b8c2ef981
Source dataset
uspto-grants-2016_04
Patent number
US09309216B2

Reaction notes

Loading…