Triphenylphosphine → (R)-methyl 2-(5-oxo-1,6-naphthyridin-6(5H)-yl)propanoate

HRID 219293Notes

Reaction equation

[O:1]=[C:2]1[N:11]([C@H:12]([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[CH:10]=[CH:9][C:8]2[N:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.N1C2C=CNC(=O)C=2C=CC=1.O[C@@H](C)C(OC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.CO.C(Cl)Cl>[NH4+:7].[OH-:1].[O:1]=[C:2]1[N:11]([C@H:12]([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[CH:10]=[CH:9][C:8]2[N:7]=[CH:6][CH:5]=[CH:4][C:3]1=2

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-methyl 2-(5-oxo-1,6-naphthyridin-6(5H)-yl)propanoate Dissolved 1,6-naphthyridin-5(6H)-one (10.6 g, 73 mmol), (S)-methyl 2-hydroxypropanoate (8.6 ml, 91 mmol) and triphenylphosphine (30 g, 116 mmol) in 144 mL THF (0.5M) and cooled to 0° C. Then added DEAD (17 ml, 109 mmol) dropwise, monitoring temperature so as not to exceed 5° C. Then let warm to room temperature over 1 hr, where reaction was complete by LCMS. The reaction was concentrated on silica and purified via MPLC, first with a gradient of Hexanes:EtOAc (removes most of PPh3O); then gradient of 100% DCM to 90% DCM:10% MeOH:1% NH4OH to yield (R)-methyl 2-(5-oxo-1,6-naphthyridin-6(5H)-yl)propanoate (16 g, 95% yield) where the ee was confirmed to be >95%.

Workup

customto exceed 5° C
temperatureThen let warm to room temperature over 1 hr
customwhere reaction
concentrationThe reaction was concentrated on silica
custompurified via MPLC, first with a gradient of Hexanes
customEtOAc (removes most of PPh3O)

Sources & evidence

ORD record: ord-03cfb194dad14c3faac3d3c1fd0c12df
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198448B2

Reaction notes

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