Triphenylphosphine → 6-{(SR)-1-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

HRID 906871Notes

Reaction equation

HRID 906871 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1.[CH2:51]([N:58]1[CH2:62][CH:61]([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[C:65]([Cl:70])[CH:64]=2)[CH:60]([CH:71](O)[CH3:72])[CH2:59]1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C1COCC1>[CH2:51]([N:58]1[CH2:62][CH:61]([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[C:65]([Cl:70])[CH:64]=2)[CH:60]([CH:71]([O:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=2)[CH3:72])[CH2:59]1)[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5387121Dibenzyl azodicarboxylateHCID 70621976-HydroxynicotinonitrileHCID 66999712(RS)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethanol

Product 1

HCID 669994036-{(SR)-1-[(3RS,4SR)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrileYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of PPh3 (PPh3 polymer bound, 3 mmol PPh3/g resin) (1.97 g) in THF (300 mL) at 0° C. were added 6-hydroxy-nicotinonitrile (0.61 g, 5.1 mmol) and then DBAD (1.10 g). After 5 minutes was added (RS)-1-[(3RS,4SR)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethanol (1.20 g, 3.4 mmol, described herein above). The reaction mixture was stirred over night at RT, filtered on celite and concentrated under vacuo. Extraction with EtOAc/aq.NaOH 1M, followed by column chromatography (SiO2, EtOAc/H, 1:4) yielded 1.02 g (66%) of the title compound as a colorless oil. ES-MS m/e: 452.0 (M+H+).

Workup

  1. filtrationfiltered on celite
  2. concentrationconcentrated under vacuo
  3. extractionExtraction with EtOAc/aq

Sources & evidence

ORD record
ord-b045759812824766a19c1f14b1ae0411
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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