Triphenylphosphine → (5R)-5-[(E)-2-[3-chloro-4-(tetrahydro-2H-pyran-4-yloxy)phenyl]-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

HRID 70631

Reaction equation

HRID 70631 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:41][C:42]1[CH:43]=[C:44](/[C:49](/[C:57]2[CH:62]=[CH:61][C:60]([CH:63]3[CH2:65][CH2:64]3)=[C:59]([O:66][CH3:67])[N:58]=2)=[CH:50]\[C@@H:51]2[NH:55][C:54](=[O:56])[CH2:53][CH2:52]2)[CH:45]=[CH:46][C:47]=1O>C1(C)C=CC=CC=1.O1CCCC1>[Cl:41][C:42]1[CH:43]=[C:44](/[C:49](/[C:57]2[CH:62]=[CH:61][C:60]([CH:63]3[CH2:64][CH2:65]3)=[C:59]([O:66][CH3:67])[N:58]=2)=[CH:50]\[C@@H:51]2[NH:55][C:54](=[O:56])[CH2:53][CH2:52]2)[CH:45]=[CH:46][C:47]=1[O:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 74956Tetrahydro-4H-pyran-4-olHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 67398720(5R)-5-[(E)-2-(3-chloro-4-hydroxyphenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Product 1

HCID 67400214(5R)-5-[(E)-2-[3-chloro-4-(tetrahydro-2H-pyran-4-yloxy)phenyl]-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tetrahydro-4-pyranol (127 mg), a 2.2 M solution of diisopropyl azodicarboxylate in toluene (0.655 mL) and triphenylphosphine (326 mg) were added to a solution of (5R)-5-[(E)-2-(3-chloro-4-hydroxyphenyl)-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one (160 mg) in tetrahydrofuran (3 mL), and the mixture was stirred at room temperature for four hours. The reaction solution was concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give (5R)-5-[(E)-2-[3-chloro-4-(tetrahydro-2H-pyran-4-yloxy)phenyl]-2-(5-cyclopropyl-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a colorless amorphous (120 mg, 61%).

Workup

  1. concentrationThe reaction solution was concentrated
  2. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1)

Sources & evidence

ORD record
ord-3e5420e059944cd28496c22459623ef9
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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