(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethyloxazol-5-yl)methanone → 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(2,4-dimethyloxazol-5-yl)ethanol

HRID 526861Notes

Reaction equation

HRID 526861 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:14]3[O:18][C:17]([CH3:19])=[N:16][C:15]=3[CH3:20])=[O:13])[CH:10]=2)[N:5]=[C:4]([O:21][CH3:22])[C:3]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1.[Li][CH3:35]>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:14]3[O:18][C:17]([CH3:19])=[N:16][C:15]=3[CH3:20])([OH:13])[CH3:35])[CH:10]=2)[N:5]=[C:4]([O:21][CH3:22])[C:3]=1[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:33])[F:32])=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 86715638(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethyloxazol-5-yl)methanone2×HCID 178418348HCID 178418348, compound

Product 1

HCID 1180061971-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(2,4-dimethyloxazol-5-yl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a flask containing (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethyloxazol-5-yl)methanone (0.225 g, 0.474 mmol, Intermediate 11: step b) was added THF (15 mL). The solution was cooled to −78° C. and MeLi (1.6 M in Et2O, 0.36 mL, 0.58 mmol) was introduced which resulted in an immediate light orange homogeneous mixture. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (4×30 mL) and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (10% CH3CN-DCM increasing to 25% CH3CN and then to 5% MeOH) provided the title compound as a pale yellow amorphous solid. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J=1.9 Hz, 1H), 7.81 (d, J=8.7 Hz, 1H), 7.61 (dd, J=8.7, 2.1 Hz, 1H), 7.50 (d, J=8.1 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 4.35 (s, 2H), 4.07 (s, 3H), 2.57 (s, 1H), 2.39 (s, 3H), 1.99 (s, 3H), 1.92 (s, 3H); MS (ESI): mass calcd. for C25H22ClF3N2O3, 490.1, m/z found 491.1 [M+H]+. 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(2,4-dimethyloxazol-5-yl)ethanol was purified by chiral chromatography (Chiralpak AD-H, solvent: 95% heptane/5% ethanol), to give 2 enantiomers. The first eluting enantiomer was Example 10b and the second eluting enantiomer was Example 10c.

Workup

  1. customresulted in an immediate light orange homogeneous mixture
  2. customAfter 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution
  3. extractionThe aqueous portion was extracted with EtOAc (4×30 mL)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5a473742ad944ca4b76feffd7617b3e4
Source dataset
uspto-grants-2016_05
Patent number
US09346782B2

Reaction notes

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