Methyl morpholine oxide → (+/-)-2-(2,3-Dihydroxypropoxy)-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrile

HRID 640724Notes

Reaction equation

HRID 640724 reaction equation
[CH2:1]([O:4][C:5]1[C:14]([C:15]#[N:16])=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:24][CH3:25])[CH:11]=2)[N:6]=1)[CH:2]=[CH2:3].C[N+]1([O-])CC[O:30]CC1.CC(O)(C)C.C1COCC1.[OH2:44]>O.CCOC(C)=O.O=[Os](=O)(=O)=O>[OH:44][CH:2]([CH2:3][OH:30])[CH2:1][O:4][C:5]1[C:14]([C:15]#[N:16])=[C:13]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:24][CH3:25])[CH:11]=2)[N:6]=1

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 114048472-(Allyloxy)-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrileHCID 22124471t-Butanol tetrahydrofuran water

Product 1

HCID 11280099(+/-)-2-(2,3-Dihydroxypropoxy)-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrile

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(allyloxy)-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrile (140 mg, 0.419 mmol) in 10 mL of tBuOH:THF:water (10:3:1) was added N-methylmorpholine N-oxide (49 mg, 0.42 mmol), followed by a solution of OsO4 (106 mg, 0.42 mmol) in water (ca. 0.5 mL). After stirring for 18 hours, the reaction was diluted with EtOAc, washed with saturated NaHCO3 solution, 10% citric acid solution and brine, and the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue (144 mg) was subjected to preparative chiral HPLC through a Chiralcel OD column (85% hexanes containing 0.1% diethylamine:EtOH). The first eluting peak was collected and concentrated in vacuo to provide the titled product. 1H-NMR (500 MHz, CDCl3) δ 7.81 (d, J=9.0 Hz, 1H), 7.70 (ddd, J=8.1, 8.1, 5.6 Hz, 1H), 7.44 (dd, J=9.0, 2.9 Hz, 1H), 7.30 (ddd, J=8.6, 2.4, 1.0 Hz, 1H), 7.25 (m, 1H), 7.19 (br d, J=8.6 Hz, 1H), 6.83 (d, J=2.9 Hz, 1H), 4.68-4.76 (m, 2H), 4.19 (m, 1H), 3.84 (dd, J=11.6, 4.1 Hz, 1H), 3.79 (dd, J=11.6, 5.4 Hz, 1H), 3.74 (s, 3H) ppm. HRMS (ES) exact mass calculated for C20H18FN2O4 (M+H+): 369.1245. Found 369.1195.

Workup

  1. washwashed with saturated NaHCO3 solution, 10% citric acid solution and brine
  2. dry with materialthe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe first eluting peak was collected
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c2756a85274c4570a2edd5682be80dbd
Source dataset
uspto-grants-2010_04
Patent number
US07692017B2

Reaction notes

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