Sodium Iodide → 8-(benzyloxy)-5-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}ethyl)quinolin-2(1H)-one

HRID 1966652Notes

Reaction equation

HRID 1966652 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21]Br)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:31][C:32]([F:48])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:33][O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][NH2:41].C(=O)(O)[O-].[Na+].[I-].[Na+]>CS(C)=O.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:21][NH:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][O:34][CH2:33][C:32]([F:31])([F:48])[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 15606253(R)-8-(benzyloxy)-5-(2-bromo-1-((tert-butyldimethylsilyl)oxy)ethyl)quinolin-2(1H)-oneHCID 509930806-(2,2-Difluoro-2-phenylethoxy)-1-hexanamine

Product 1

HCID 509930818-(benzyloxy)-5-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}ethyl)quinolin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (4.80 g, 9.83 mmol) and Intermediate 9 (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with diethyl ether (2×20 mL)
  3. washThe combined organic extracts were washed with water (2×10 mL) and brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-c941aa1eaba8436ab0d7c7ebe864cbfe
Source dataset
uspto-grants-2013_04
Patent number
US08420669B2

Reaction notes

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