2,6-Lutidine → (R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-one

HRID 332640Notes

Reaction equation

HRID 332640 reaction equation
N1C(C)=CC=CC=1C.[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@@H:28]([OH:31])[CH2:29][Br:30])=[C:21]2[C:26]=1[NH:25][C:24](=[O:27])[CH:23]=[CH:22]2)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.FC(F)(F)S(O[Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])(=O)=O>C(Cl)Cl>[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@@H:28]([O:31][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH2:29][Br:30])=[C:21]2[C:26]=1[NH:25][C:24](=[O:27])[CH:23]=[CH:22]2)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 115308845-((1R)-2-bromo-1-hydroxyethyl)-8-phenylmethoxy-1H-quinolin-2-one

Product 1

HCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneYield 85.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,6-Lutidine (6.9 mL, 59.5 mmol) was added to a solution of (R)-8-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)quinolin-2(1H)-one (10.1 g, 27.0 mmol) in DCM (100 mL) at 0° C. The reaction mixture was stirred for 5 minutes and then tert-butyldimethylsilyl trifluoromethanesulfonate (13.0 mL, 56.8 mmol) was added dropwise over 15 minutes. The mixture was stirred at 0° C. for 30 minutes, followed by RT overnight. After this time the reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with DCM (×3). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated under reduced pressure. Iso-hexane (500 mL) was added to the crude material and the resulting solid collected by filtration. The solid was recrystallised from ethyl acetate and petroleum ether (40:60) to afford the title compound (11.3 g, 85%).

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 minutes
  2. waitfollowed by RT overnight
  3. customAfter this time the reaction was quenched with saturated aqueous sodium bicarbonate solution
  4. extractionextracted with DCM (×3)
  5. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionIso-hexane (500 mL) was added to the crude material
  9. filtrationthe resulting solid collected by filtration
  10. customThe solid was recrystallised from ethyl acetate and petroleum ether (40:60)

Sources & evidence

ORD record
ord-fcdd131278784c58b436758c5a8dd012
Source dataset
uspto-grants-2014_11
Patent number
US08877774B2

Reaction notes

Loading…