4-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]benzene-1,3-diol → 4-{[(6R)-3-fluoro-6-methylphenanthridin-5(6H)-yl]carbonyl}benzene-1,3-diol

HRID 731995Notes

Reaction equation

HRID 731995 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11]([CH:12]([CH3:26])[N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=4[OH:25])=[O:17])[C:14]=2[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11]([C@@H:12]([CH3:26])[N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=4[OH:25])=[O:17])[C:14]=2[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3

Participants

3

Reactant 1

HCID 115303814-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]benzene-1,3-diol

Product 1

HCID 115738404-{[(6R)-3-fluoro-6-methylphenanthridin-5(6H)-yl]carbonyl}benzene-1,3-diol

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

The enantiomers of 4-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]benzene-1,3-diol (800 mg, 2.29 mmol) were separated by automated, preparative, normal phase, chiral chromatography on a Chiralpak AS (20 mm×250 mm) column eluting with 15% isopropyl alcohol in hexane at a flow rate of 20 mL/min with. The fractions containing the first peak were combined and concentrated in vacuo, to provide one peak (99.9%) with a retention time of 7.971 minutes was isolated as a white solid (224 mg, 56% based upon a 1:1 ratio of enantiomers with a theoretical maximum amount of 400 mg). mp 184-187° C.; [α]D25=−665° (c=0.0104 g/mL, CHCl3); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (d, J=6.73 Hz, 3 H) 5.65 (m, J=6.73 Hz, 1 H) 6.16 (d, J=1.81 Hz, 1 H) 6.22 (dd, J=8.41, 2.20 Hz, 1 H) 6.75 (d, J=9.83 Hz, 1 H) 6.98 (d, J=8.28 Hz, 1 H) 7.04 (td, J=8.67, 2.59 Hz, 1 H) 7.33 (m, 2 H) 7.39 (m, 1 H) 7.90 (d, J=7.76 Hz, 1 H) 7.94 (dd, J=8.79, 6.21 Hz, 1 H) 9.62 (s, 1 H) 9.70 (s, 1 H); MS (ESI) m/z 350 ([M+H]+); MS (ESI) m/z 348 ([M−H]−); HRMS: calcd for C21H16FNO3, 349.1114 (M), 350.1187 ([M+H]+); found (ESI+), 350.1181.

Workup

  1. washeluting with 15% isopropyl alcohol in hexane at a flow rate of 20 mL/min with
  2. additionThe fractions containing the first peak
  3. concentrationconcentrated in vacuo
  4. customto provide one peak (99.9%) with a retention time of 7.971 minutes
  5. customwas isolated as a white solid (224 mg, 56%

Sources & evidence

ORD record
ord-650f908d678d477dad5cff6e3bd511ee
Source dataset
uspto-grants-2009_09
Patent number
US07585871B2

Reaction notes

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