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1,4-Dioxane → ethyl (3S)-1-(2-fluoro-4-pyridin-4-ylphenyl)piperidine-3-carboxylate

HRID 656341
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HRID 656341 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[F:14].Cl.[NH:16]1[CH2:21][CH2:20][CH2:19][C@H:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:17]1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:14][C:3]1[CH:4]=[C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:6]=[CH:7][C:2]=1[N:16]1[CH2:21][CH2:20][CH2:19][C@H:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:17]1
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참가 물질

7

반응물 5

HCID 312751,4-DioxaneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 45074034(S)-Ethyl piperidine-3-carboxylate hydrochlorideHCID 666841274-(4-Bromo-3-fluorophenyl)pyridine

생성물 1

HCID 66742908ethyl (3S)-1-(2-fluoro-4-pyridin-4-ylphenyl)piperidine-3-carboxylate

시약·촉매·용매 1

HCID 167845palladium(II) acetate촉매

실험 절차

A mixture of 4-(4-bromo-3-fluorophenyl)pyridine (190 mg, 0.00075 mol), ethyl (3S)-piperidine-3-carboxylate hydrochloride (180 mg, 0.00090 mol), sodium tert-butoxide (140 mg, 0.0015 mol), palladium acetate (5 mg, 0.00002 mol) and 2-(di-tert-butylphosphino)biphenyl (7 mg, 0.00002 mol) was evacuated and charged with nitrogen and 1,4-dioxane (5 mL, 0.06 mol). The resulting mixture was refluxed overnight. After cooling to ambient temperature, the mixture was filtered and the filtrate was adjusted with TFA to pH=7.0 and purified by CombiFlash (ethyl acetate in hexanes: 60%) to afford the desired product. LCMS: m/z 329.2 (M+H)+.

후처리

  1. customwas evacuated
  2. temperatureThe resulting mixture was refluxed overnight
  3. filtrationthe mixture was filtered
  4. custompurified by CombiFlash (ethyl acetate in hexanes: 60%)

출처 및 근거

ORD 기록
ord-fe4783c139e942b5907ca49137408f72
출처 데이터셋
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08071624B2

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