Triphenylphosphine → (R)-3-(6-Cyclopropoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

HRID 533921Notes

Reaction equation

HRID 533921 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][CH2:15][C@H:14]([OH:17])[C:13]2=[O:18])[CH:5]=[C:6]2[C:10]=1[CH2:9][CH2:8][C:7]2=[O:11].[CH:19]1([O:22][C:23]2[N:28]=[CH:27][C:26](O)=[CH:25][CH:24]=2)[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>C1COCC1>[CH:19]1([O:22][C:23]2[N:28]=[CH:27][C:26]([O:17][C@@H:14]3[CH2:15][CH2:16][N:12]([C:4]4[CH:5]=[C:6]5[C:10](=[C:2]([F:1])[CH:3]=4)[CH2:9][CH2:8][C:7]5=[O:11])[C:13]3=[O:18])=[CH:25][CH:24]=2)[CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 867150946-(Cyclopropyloxy)-3-pyridinolHCID 86715111(S)-1-(7-Fluoro-3-oxo-indan-5-yl)-3-hydroxy-pyrrolidin-2-one

Product 1

HCID 74767737(R)-3-(6-Cyclopropoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)-1-(7-fluoro-3-oxo-2,3-dihydro-1H-inden-5-yl)-3-hydroxy-pyrrolidin-2-one (80 mg), 6-cyclopropoxy-pyridine-3-ol (53.4 mg), triphenylphosphine (polymer, 126 mg) and THF (1.5 mL) was added DIAD (97 mg). The mixture was shaken for 2 hours and filtered. The filtrate was concentrated and the residue purified by preparative HPLC to provide Example 3-13. 1H-NMR (400 MHz, DMSO) δ 8.02 (1H, d, J=3.1 Hz), 7.99 (1H, d, J=11.1 Hz), 7.78 (1H, s), 7.55 (1H, dd, J=9.0, 3.1 Hz), 6.83 (1H, d, J=9.0 Hz), 5.25 (1H, dd, J=8.3, 8.3 Hz), 4.13 (1H, m), 3.97 (1H, m), 3.86 (1H, m), 3.10 (2H, m), 2.72 (2H, m), 2.70 (1H, m), 2.14 (1H, m), 0.74 (2H, m), 0.64 (2H, m).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. customthe residue purified by preparative HPLC
  4. customto provide Example 3-13

Sources & evidence

ORD record
ord-d7b6ac96ffc94f85947b64c180eca779
Source dataset
uspto-grants-2014_10
Patent number
US08853412B2

Reaction notes

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