Potassium Carbonate → {2-[4-(4-Cyanopyridin-2-yloxy)phenyl]ethyl}carbamic acid tert-butyl ester

HRID 1409290Notes

Reaction equation

HRID 1409290 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][N:26]=1)[C:22]#[N:23].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:19]2[CH:20]=[C:21]([C:22]#[N:23])[CH:24]=[CH:25][N:26]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 59730249{2-[4-(4-Cyanopyridin-2-yloxy)phenyl]ethyl}carbamic acid tert-butyl esterYield 73.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
137.5 °C

Procedure

[2-(4-Hydroxyphenyl)-ethyl]-carbamic acid tert-butyl ester (5.31 g, 22.4 mmol) and 2-chloroisonicotinonitrile (3.27 g, 22.4 mmol) were dissolved with magnetic stirring in dimethyl sulfoxide (DMSO; 50 mL) in a 250 mL round bottom flask equipped with a reflux condenser and a dry nitrogen line at 25° C. To the solution was added K2CO3 (6.0 g, 43.5 mmol), and the reaction mixture was slowly heated to 135-140° C. over 1 h. The reaction was filtered, concentrated in vacuo, and diluted with H2O (500 mL). The precipitate which formed was collected by suction filtration, dissolved in CH2Cl2 and treated with decolorizing carbon. The mixture was filtered and concentrated in vacuo to afford {2-[4-(4-cyanopyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (5.57 g) as a beige solid: mp 92-96° C.; 1H-NMR (CDCl3) δ 8.32 (d, J=5.3 Hz, 1H), 7.26 (m, 2H), 7.20 (dd, J=5.1, 0.8 Hz, 1H), 7.16 (m, 1H), 7.10-7.04 (m, 3H), 3.40 (br m, 2H), 2.83 (m, 2H), 1.45 (s, 9H); ESIMS m/z 284.2 ([M−C4H8+H]+). This material was used without further purification in the next step.

Workup

  1. customequipped with a reflux condenser
  2. customat 25° C
  3. filtrationThe reaction was filtered
  4. concentrationconcentrated in vacuo
  5. additiondiluted with H2O (500 mL)
  6. customThe precipitate which formed
  7. filtrationwas collected by suction filtration
  8. dissolutiondissolved in CH2Cl2
  9. additiontreated with decolorizing carbon
  10. filtrationThe mixture was filtered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-be026dd01b7a489fb63398094db7a28b
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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