Triethylamine → HCID 86301333, compound

HRID 1748386Notes

Reaction equation

HRID 1748386 reaction equation
[FH:1].F.F.C(N(CC)CC)C.C(N(CC)CC)C.[F:18][C:19]1[CH:40]=[CH:39][C:22]([CH2:23][O:24][C:25]2[CH:34]=[C:33]3[C:28]([CH:29]=[C:30]([C:35](O)([CH3:37])[CH3:36])[CH:31]=[N:32]3)=[CH:27][CH:26]=2)=[CH:21][CH:20]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[F:18][C:19]1[CH:40]=[CH:39][C:22]([CH2:23][O:24][C:25]2[CH:34]=[C:33]3[C:28]([CH:29]=[C:30]([C:35]([F:1])([CH3:37])[CH3:36])[CH:31]=[N:32]3)=[CH:27][CH:26]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 86301020HCID 86301020, compound

Product 1

HCID 86301333HCID 86301333, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

XtalFluor® (66.19 mg, 0.29 mmol) was transferred to a flask and put under nitrogen, then DCM (2 mL) was added via syringe. The reaction was cooled to 0° C. in an ice bath then triethylamine trihydrofluoride (62.76 μl, 0.39 mmol) and triethylamine (26.7 μL, 0.19 mmol) were added via syringe. The reaction was stirred until all solids dissolved completely then was cooled to −78° C. in a dry ice/acetone bath. A solution of 2-(7-((4-fluorobenzyl)oxy)quinolin-3-yl)propan-2-ol (Example 27, 60 mg, 0.19 mmol) in DCM (1 mL) was added via syringe then the reaction was warmed to 0° C. and allowed to stir for 1 hour. Upon completion, a solution of NaHCO3 (sat aq.) and EtOAc was added. The combined organics were separated and washed with a 50% aq. bleach solution. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification (FCC, SiO2, 0-25%, EtOAc/Hexanes,), and a second purification with preparative HPLC (Shimadzu SCL-10 VP, ACN/H2O, 25-90% (0.1% TFA)) afforded the title compound as a pure solid (18.2 mg, 22%). 1H NMR (400 MHz, CDCl3) δ 9.08 (d, J=1.8 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.77 (d, J=9.0 Hz, 1H), 7.53 (dd, J=5.4, 8.4 Hz, 2H), 7.43 (d, J=9.0 Hz, 1H), 7.29 (s, 1H), 7.12 (t, J=8.7 Hz, 2H), 5.35 (s, 2H), 1.99-1.63 (m, 6H). [M+H]=314.1.

Workup

  1. customXtalFluor® (66.19 mg, 0.29 mmol) was transferred to a flask
  2. dissolutiondissolved completely
  3. temperaturethen was cooled to −78° C. in a dry ice/acetone bath
  4. temperaturethe reaction was warmed to 0° C.
  5. stirringto stir for 1 hour
  6. customThe combined organics were separated
  7. washwashed with a 50% aq. bleach solution
  8. dry with materialThe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification (FCC, SiO2, 0-25%, EtOAc/Hexanes,)
  12. customa second purification with preparative HPLC (Shimadzu SCL-10 VP, ACN/H2O, 25-90% (0.1% TFA))

Sources & evidence

ORD record
ord-2e987c818716422a95db5442ca841621
Source dataset
uspto-grants-2015_10
Patent number
US09150572B2

Reaction notes

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