3-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenol → 3-{[(6R)-3-fluoro-6-methylphenanthridin-5(6H)-yl]carbonyl}phenol

HRID 731987Notes

Reaction equation

HRID 731987 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11]([CH:12]([CH3:25])[N:13]([C:16]([C:18]4[CH:19]=[C:20]([OH:24])[CH:21]=[CH:22][CH:23]=4)=[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]([CH3:25])[N:13]([C:16]([C:18]4[CH:19]=[C:20]([OH:24])[CH:21]=[CH:22][CH:23]=4)=[O:17])[C:14]=2[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=3

Participants

3

Reactant 1

HCID 115009123-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenol

Product 1

HCID 116313523-{[(6R)-3-fluoro-6-methylphenanthridin-5(6H)-yl]carbonyl}phenol

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

The enantiomers of 3-[(3-fluoro-6-methylphenanthridin-5(6H)-yl)carbonyl]phenol (660 mg, 1.98 mmol) were separated by automated, preparative, normal phase, chiral chromatography on a Chiralpak AD (20 mm×250 mm) column eluting with 100% acetonitrile 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 2.708 minutes was isolated as a white solid (270 mg, 82% based upon a 1:1 ratio of enantiomers with a theoretical maximum amount of 330 mg). [α]D25 =−545° (c=0.0105 g/mL, CHCl3); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (d, J=6.98 Hz, 3 H) 5.66 (q, J=6.38 Hz, 1 H) 6.69 (d, J=7.24 Hz, 2 H) 6.72 (s, 1 H) 6.83 (ddd, J=8.15, 2.46, 0.78 Hz, 1 H) 7.09 (td, J=8.67, 2.59 Hz, 1 H) 7.16 (t, J=7.89 Hz, 1 H) 7.37 (m, 2 H) 7.44 (td, 1 H) 7.96 (d, J=7.76 Hz, 1 H) 8.00 (dd, J=8.79, 6.47 Hz, 1 H) 9.66 (s, 1 H) MS (ESI) m/z 334 ([M+H]+); MS (ESI) m/z 332 ([M−H]−); HRMS: calcd for C21H16FNO2, 333.1165 (M), 334.12379 ([M+H]+); found (ESI+), 334.12345.

Workup

  1. washeluting with 100% acetonitrile 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 2.708 minutes
  5. customwas isolated as a white solid (270 mg, 82%

Sources & evidence

ORD record
ord-d860c5a7eb73463196c56a629d940d4f
Source dataset
uspto-grants-2009_09
Patent number
US07585871B2

Reaction notes

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