Sodium hydride → HCID 70982247, compound

HRID 2175225Notes

Reaction equation

HRID 2175225 reaction equation
[H-].[Na+].[CH3:3][C:4]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11][CH2:12][OH:13].[Br:14][C:15]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:16]=1[CH2:17][CH2:18][CH2:19][N:20]2[C:25](=[O:28])[CH2:26]Cl>C1COCC1.C(=O)(O)[O-].[Na+]>[Br:14][C:15]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:16]=1[CH2:17][CH2:18][CH2:19][N:20]2[C:25](=[O:28])[CH2:26][O:13][CH2:12][CH2:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([CH3:10])[C:4]=1[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 33941HCID 33941, compoundHCID 86712578HCID 86712578, compound

Product 1

HCID 70982247HCID 70982247, compoundYield 11.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of sodium hydride (35.1 mg, 1.46 mmol) in anhydrous THF (3.0 mL) under nitrogen was added 2-(2,3-dimethylphenyl)ethanol (220 mg, 1.46 mmol). The reaction mixture was stirred at room temperature for 15 min and then a solution of 1-(5-bromo-3,4-dihydroquinolin-1(2H)-yl)-2-chloroethanone (352 mg, 1.22 mmol) in anhydrous THF (3.0 mL) was added. The resulting mixture was stirred at room temperature for 18 h. After this time, the reaction mixture was diluted with saturated sodium bicarbonate (55 mL) and then extracted with ethyl acetate (60 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by preparative HPLC (PHENOMENEX® Axia Luna, 5μ, C18, 30×250 mm; 25 min gradient from 80% A:20% B to 0% A:100% B and 5 min 100% B (A=90% H2O/10% MeOH+0.1% TFA); (B=90% MeOH/10% H2O+0.1% TFA); detection at 220 nm) to afford the title compound (55 mg, 11% yield) as white powder. LCMS, [M+H]+=402.1. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J=8.0 Hz, 1H), 7.30 (br. s, 1H), 7.02-6.96 (m, 4H), 4.20 (s, 2H), 3.74-3.69 (m, 2H), 3.66 (t, J=7.4 Hz, 2H), 2.92 (t, J=7.4 Hz, 2H), 2.78 (t, J=6.9 Hz, 2H), 2.24 (s, 3H), 2.18 (s, 3H), 1.99-1.90 (m, 2H).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 18 h
  2. extractionextracted with ethyl acetate (60 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by preparative HPLC (PHENOMENEX® Axia Luna, 5μ, C18, 30×250 mm
  7. custom25 min gradient
  8. custom100% B and 5 min 100% B

Sources & evidence

ORD record
ord-b2f4ca31365f438bb8da52eeec89da27
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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