Triethylamine → HCID 68282874, compound

HRID 1473142Notes

Reaction equation

HRID 1473142 reaction equation
[CH2:1]([Si:3]([C:8]#[CH:9])([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].C(N(CC)CC)C.Cl[C:18]1[C:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:22][CH:21]=[CH:20][N:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:8]([Si:3]([C:6]#[C:7][C:18]1[C:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:22][CH:21]=[CH:20][N:19]=1)([CH2:4][CH3:5])[CH2:1][CH3:2])[CH3:9]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 637947(Triethylsilyl)acetyleneHCID 19771888(2-Chloro-pyridin-3-yl)-acetic acid methyl ester

Product 1

HCID 68282874HCID 68282874, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of triethylsilyl acetylene (0.579 mL, 3.23 mmol) in degassed DMF (3 mL) and triethylamine (0.901 mL, 6.47 mmol) were added to a mixture of methyl 2-(2-chloropyridin-3-yl)acetate (I118) (0.200 g, 1.08 mmol), Pd(PPh3)2Cl2 (75.6 mg, 0.108 mmol), Cu(I)I (30.8 mg, 0.162 mmol) and triphenylphosphine (42.4 mg, 0.162 mmol) in degassed DMF (4 mL) and the resulting mixture was heated at 90° C. for 20 hours. The cooled mixture was diluted with EtOAc and passed through a plug of celite, washing with ethyl acetate (100 mL). Water (75 mL) was added to the filtrate and the layers separated. The aqueous layer was extracted with EtOAc (2×75 mL). The combined organic extracts were washed with brine (100 mL) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a dark brown residue. The residue was purified by column chromatography on silica gel (0-50% EtOAc in cyclohexane) to yield the title compound (I119) (0.353 g) as a brown oil which was used without further purification; 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=4.8, 1.6 Hz, 1H), 7.62 (dd, J=7.8, 1.6 Hz, 1H), 7.22 (dd, J=7.8, 4.8 Hz, 1H), 3.86 (s, 2H), 3.70 (s, 3H), 1.05 (t, J=7.9 Hz, 9H), 0.75-0.67 (m, 6H). LCMS Method C: rt 6.55 min; m/z 290 [M+H]+.

Workup

  1. washwashing with ethyl acetate (100 mL)
  2. additionWater (75 mL) was added to the filtrate
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with EtOAc (2×75 mL)
  5. washThe combined organic extracts were washed with brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customto give a dark brown residue
  10. customThe residue was purified by column chromatography on silica gel (0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-9702554306c7497f817e940a5777ed44
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…