Potassium Carbonate → HCID 90047095, compound
Reaction equation
[C:1]([S:5]([C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[OH:18])[N:14]=[CH:13][CH:12]=[C:11]2[Cl:19])(=[O:7])=[O:6])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[F:26][CH:27]([F:30])[CH2:28]I>>[C:1]([S:5]([C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:28][CH:27]([F:30])[F:26])[N:14]=[CH:13][CH:12]=[C:11]2[Cl:19])(=[O:6])=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 6-(tert-butylsulfonyl)-4-chloroquinolin-7-ol (100 mg, 0.334 mmol) was added K2CO3 (138 mg, 1.001 mmol) followed by 1,1-difluoro-2-iodoethane (44.1 μl, 0.500 mmol). This was heated to 60° C. overnight. LCMS showed incomplete conversion. Additional 1,1-difluoro-2-iodoethane (44.1 μl, 0.500 mmol) was added and the reaction was stirred at 60° C. for 5 hr. Reaction was still not complete by LCMS, so another aliquot of 1,1-difluoro-2-iodoethane (44.1 μl, 0.500 mmol) was added and the reaction was stirred at 60° C. overnight again. LCMS showed complete and clean conversion to the desired product. The crude sample was purified via Biotage normal phase chromatography (25 g SNAP column, 0% -50%, 50% hex/EtOAc). The pure product containing-fractions were combined and concentrated leading to the product as an off-white solid: 6-(tert-butylsulfonyl)-4-chloro-7-(2,2-difluoroethoxy)quinoline (88.8 mg, 0.244 mmol, 73.2% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32 (s, 9H) 4.66 (td, J=14.53, 3.54 Hz, 2H) 6.28-6.63 (m, 1H) 7.80 (d, J=4.80 Hz, 1H) 7.85 (s, 1H) 8.67 (s, 1H) 8.97 (d, J=4.80 Hz, 1H). MS: m/z: 364.1 [M+H]+.
Workup
- customReaction
- stirringthe reaction was stirred at 60° C. overnight again
Sources & evidence
- ORD record
- ord-c9d7c5d4466842dab4709c811f7d6fa8
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216965B2
Reaction notes
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