Triphenylphosphine → 1-methylcyclopropyl 4-((1R,2S)-2-{2-[4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate

HRID 1850758노트

반응식

HRID 1850758 반응식
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.O[CH2:14][CH2:15][C@@H:16]1[CH2:18][C@@H:17]1[CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]2([CH3:31])[CH2:30][CH2:29]2)=[O:26])[CH2:21][CH2:20]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1.C(OCC)(=O)C.O>[CH3:12][O:11][C:9](=[O:10])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:14][CH2:15][C@@H:16]2[CH2:18][C@@H:17]2[CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]3([CH3:31])[CH2:30][CH2:29]3)=[O:26])[CH2:21][CH2:20]2)=[CH:7][CH:6]=1

참가 물질

8

반응물 4

HCID 11776TriphenylphosphineHCID 518900Benzeneacetic acid, 4-hydroxy-, methyl esterHCID 5363146Diisopropyl azodicarboxylateHCID 708189561-methylcyclopropyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate

생성물 1

HCID 708560031-methylcyclopropyl 4-((1R,2S)-2-{2-[4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Methyl (4-hydroxyphenyl)acetate (37 mg, 0.22 mmol), 1-methylcyclopropyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (60 mg, 0.22 mmol), and triphenylphosphine (88 mg, 0.34 mmol) were dissolved in tetrahydrofuran (1 mL) under an atmosphere of nitrogen and cooled at 0° C. DIAD (68 mg, 0.34 mmol) was added and the resulting mixture was warmed to RT and stirred overnight. The mixture was diluted with ethyl acetate (10 mL) and water (5 mL), and the layers were separated. The organic layer was washed with brine (2×10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (24 g of silica gel, ISCO, eluted with a gradient 0-100% ethyl acetate in Hexane) to afford the title compound. HPLC/MS; 1.27 min, 438 (M+Na)+.

후처리

  1. temperaturethe resulting mixture was warmed to RT
  2. customthe layers were separated
  3. washThe organic layer was washed with brine (2×10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (24 g of silica gel, ISCO
  8. washeluted with a gradient 0-100% ethyl acetate in Hexane)

출처 및 근거

ORD 기록
ord-ebdf0516e19b451ba357c2a1bdec8796
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957062B2

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