Triethylamine → methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-acetate

HRID 2186396Notes

Reaction equation

HRID 2186396 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.I[C:21]1[S:22][CH:23]=[CH:24][CH:25]=1.[O:26]=[C:27]([C:44]1[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([O:54][CH3:55])[CH:52]=2)[N:47]=[CH:46][CH:45]=1)[CH2:28][CH2:29][C@@H:30]1[CH2:35][CH2:34][N:33]([CH2:36][C:37]#[CH:38])[CH2:32][C@@H:31]1[CH2:39][C:40]([O:42][CH3:43])=[O:41].C(N(CC)CC)C>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:26]=[C:27]([C:44]1[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([O:54][CH3:55])[CH:52]=2)[N:47]=[CH:46][CH:45]=1)[CH2:28][CH2:29][C@@H:30]1[CH2:35][CH2:34][N:33]([CH2:36][C:37]#[C:38][C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[CH2:32][C@@H:31]1[CH2:39][C:40]([O:42][CH3:43])=[O:41]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 189212-IodothiopheneHCID 86758168methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[prop-2-ynyl]piperidine-3-acetate

Product 1

HCID 86758167methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

0.263 g of triphenylphosphine and then 0.85 g of tetrakis(triphenylphosphine)palladium, 0.4 g of cuprous iodide, and 1.75 cm3 of 2-iodothiophene were added with stirring, at a temperature in the region of 20° C. and under an inert atmosphere, to a solution of 4.3 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[prop-2-ynyl]piperidine-3-acetate in 100 cm3 of acetonitrile. The mixture was stirred for 10 minutes and then 2.95 cm3 of triethylamine were added. After stirring for 48 hours at a temperature in the region of 20° C., the mixture was filtered through celite and the insoluble material was washed with 2 times 50 cm3 of acetonitrile. The filtrate was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 4.5 cm; silica volume 500 cm3), elution was carried out with pure ethyl acetate, and approximately 60-cm3 fractions were collected. The fractions corresponding to the expected product were combined. These fractions were concentrated under the above conditions. 4 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.

Workup

  1. stirringAfter stirring for 48 hours at a temperature in the region of 20° C.
  2. filtrationthe mixture was filtered through celite
  3. washthe insoluble material was washed with 2 times 50 cm3 of acetonitrile
  4. concentrationThe filtrate was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  5. customThe evaporation residue was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 4.5 cm; silica volume 500 cm3), elution
  6. customwere collected
  7. concentrationThese fractions were concentrated under the above conditions

Sources & evidence

ORD record
ord-4451ba42e31d4223b3c16e4a92e6b6c6
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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