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

HRID 526863
Notes
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Reaction equation

HRID 526863 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:14]3[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=3)=[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[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=3)([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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 86715634(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone2×HCID 178418348HCID 178418348, compound

Product 1

HCID 1180062581-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-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)(1,2-dimethyl-1H-imidazol-5-yl)methanone (408 mg, 0.86 mmol, Intermediate 8: step b) was added THF (20 mL) and the solution was cooled to −78° C. MeLi (1.6 M in Et2O, 0.6 mL, 0.96 mmol) was then introduced. After 25 minutes, the reaction mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (4×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (5% MeOH-DCM increasing to 10% MeOH) provided the title compound as a white amorphous solid. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J=1.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.2 Hz, 3H), 7.40 (d, J=8.1 Hz, 2H), 7.04 (d, J=10.7 Hz, 1H), 4.35 (s, 2H), 4.07 (s, 3H), 3.14 (s, 3H), 2.29 (s, 3H), 1.95 (s, 3H); MS (ESI): mass calcd. for C25H23ClF3N3O2, 489.1, m/z found 490.1 [M+H]+. 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)ethanol was purified by chiral chromatography (Chiracel OD (20 μM) diacel, 50×41 cm, heptane:ethanol with 2% isopropylamine (90:10)), to give 2 enantiomers. The first eluting enantiomer was Example 12b and the second eluting enantiomer was Example 12c.

Workup

  1. customthe reaction mixture was quenched with aqueous NH4Cl solution
  2. extractionthe aqueous portion was extracted with EtOAc (4×40 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-7303917ac19a41fc81549a1da7980346
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09346782B2

Reaction notes

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