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Water → methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylate

HRID 2186409
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HRID 2186409 반응식
[OH:1][CH:2]([C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][CH:19]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[CH:13])[CH2:7][C@@H:6]1[C:14]([O:16][CH3:17])=[O:15].Br[C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[C:32]=1[F:39].C(OCC)(=O)C.O>C(N(CC)CC)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>[OH:1][CH:2]([C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][CH:19]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[C:32]=2[F:39])[CH2:7][C@@H:6]1[C:14]([O:16][CH3:17])=[O:15]
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참가 물질

7

반응물 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 27363991-Bromo-2,3,5-trifluorobenzeneHCID 131723275methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate

생성물 1

HCID 131723296methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylate
수율 50.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 8471Triethylamine용매

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온도
20 °C

실험 절차

A mixture of 1.95 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate in 20 cm3 of triethylamine was stirred for 5 minutes under an inert atmosphere at a temperature in the region of 20° C. 0.284 g of tetrakis(triphenylphosphine)palladium, 0.094 9 of cuprous iodide, and 1.56 g of 1-bromo-2,3,5-trifluorobenzene were added. The mixture was stirred for 2 hours 30 minutes at a temperature in the region of 80° C. After cooling to approximately 20° C., the reaction mixture had 60 cm3 of ethyl acetate and 60 cm3 of water added. After stirring for 30 minutes, the mixture was separated by settling. After separating off the organic phase, the aqueous layer was extracted with 3 times 30 cm3 of ethyl acetate. The organic extracts were combined, washed with 3 times 30 cm3 of water, dried over sodium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μm, diameter 4 cm; 80 g), elution was carried out with pure ethyl acetate, and first a fraction of 100 cm3 was collected, followed by 20-cm3 fractions. Fractions 23 to 27 were combined and concentrated as above. 1.3 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylate were obtained in the form of a foam.

후처리

  1. stirringThe mixture was stirred for 2 hours 30 minutes at a temperature in the region of 80° C
  2. temperatureAfter cooling to approximately 20° C.
  3. additionadded
  4. stirringAfter stirring for 30 minutes
  5. customthe mixture was separated
  6. customAfter separating off the organic phase
  7. extractionthe aqueous layer was extracted with 3 times 30 cm3 of ethyl acetate
  8. washwashed with 3 times 30 cm3 of water
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  12. customThe residue obtained
  13. customwas purified by chromatography under a nitrogen pressure of 50 kPa
  14. washon a column of silica gel (particle size 20-45 μm, diameter 4 cm; 80 g), elution
  15. customfirst a fraction of 100 cm3 was collected
  16. concentrationconcentrated as above

출처 및 근거

ORD 기록
ord-e5d49d168eef45188b9a2a47a77d5fd2
출처 데이터셋
uspto-grants-2002_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06403610B1

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