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

HRID 1850758Notes

Reaction equation

HRID 1850758 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-ebdf0516e19b451ba357c2a1bdec8796
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

Loading…