Triphenylphosphine → (S)-3-[(R)-2-Benzyloxy-1-(4-chloro-2-methylphenoxy)ethyl]pyrrolidine

HRID 533379Notes

Reaction equation

HRID 533379 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C(OC([N:50]1[CH2:54][CH2:53][C@H:52]([C@H:55](O)[CH2:56][O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH2:51]1)=O)(C)(C)C>C1(C)C=CC=CC=1>[CH2:58]([O:57][CH2:56][C@@H:55]([C@H:52]1[CH2:53][CH2:54][NH:50][CH2:51]1)[O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[CH3:9])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 148554-Chloro-2-methylphenolHCID 5363146Diisopropyl azodicarboxylateHCID 66859062(S)-3-((S)-2-benzyloxy-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester

Product 1

HCID 58120255(S)-3-[(R)-2-Benzyloxy-1-(4-chloro-2-methylphenoxy)ethyl]pyrrolidine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

4-Chloro-2-methylphenol (14.1 mg, 98.9 μmol) was combined with PPh3 (26.0 mg, 98.9 μmol) dissolved in toluene (87.8 μL), and the mixture heated at 100° C. DIAD (19.5 μL, 98.9 μmol) was combined with (S)-3-((S)-2-benzyloxy-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (19.1 mg, 59.3 mmol) dissolved in toluene (58.0 μL), and slowly added to the heated mixture and stirred for two hours. The mixture was cooled to room temperature and concentrated. The residue was treated with 1.25M HCl in EtOH (474.6 μL) overnight at room temperature. The mixture was concentrated, the residue was redissolved in a mixture of MeCN (0.4 mL), AcOH (0.6 mL) and water (0.6 mL), filtered and purified by reverse phase preparative HPLC to yield the title compound as a mono-TFA salt (7.8 mg, 99% purity). MS m/z: [M+H]+ calcd for C20H24ClNO2, 346.15. found 346.2.

Workup

  1. additionslowly added to the heated mixture
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated
  4. additionThe residue was treated with 1.25M HCl in EtOH (474.6 μL) overnight at room temperature
  5. concentrationThe mixture was concentrated
  6. dissolutionthe residue was redissolved in a mixture of MeCN (0.4 mL), AcOH (0.6 mL) and water (0.6 mL)
  7. filtrationfiltered
  8. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-f0c79558b5534877ade4de3d02e56409
Source dataset
uspto-grants-2014_10
Patent number
US08853255B2

Reaction notes

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