2-Bromopropionic acid → 2-[4-(5-Chloro-2-cyanophenyl)-5-(difluoromethoxy)-2-oxopyridin-1(2H)-yl]propanoic acid

HRID 56858Notes

Reaction equation

HRID 56858 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH:17]([F:19])[F:18])=[CH:14][NH:13][C:12](=[O:20])[CH:11]=2)[CH:3]=1.CC(C)([O-])C.CC(C)([O-])C.[Mg+2].CC(C)([O-])C.[K+].Br[CH:39]([CH3:43])[C:40]([OH:42])=[O:41]>O1CCCC1>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]2[C:15]([O:16][CH:17]([F:18])[F:19])=[CH:14][N:13]([CH:39]([CH3:43])[C:40]([OH:42])=[O:41])[C:12](=[O:20])[CH:11]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 117292-Bromopropionic acid2×HCID 12040442Magnesium 2-methylpropan-2-olate2×HCID 23665647Potassium tert-butoxide2×HCID 1176056964-Chloro-2-[5-(difluoromethoxy)-2-oxo-1,2-dihydropyridin-4-yl]benzonitrile

Product 1

HCID 1176228622-[4-(5-Chloro-2-cyanophenyl)-5-(difluoromethoxy)-2-oxopyridin-1(2H)-yl]propanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

163 mg (0.55 mmol) of 4-chloro-2-[5-(difluoromethoxy)-2-oxo-1,2-dihydropyridin-4-yl]benzonitrile, 2.0 eq. of magnesium di-tert-butoxide, 1.05 eq. of potassium tert-butoxide and 1.5 eq. of 2-bromopropanoic acid (racemate) were reacted at 45° C. and worked up according to General Method 4A. Owing to incomplete conversion, the crude product was then once more reacted as described above with 1.2 eq. of magnesium di-tert-butoxide, 0.65 eq. of potassium tert-butoxide and 0.8 eq. of 2-bromopropionic acid (racemate) in 3.5 ml of tetrahydrofuran and worked up analogously. Yield: 270 mg (purity 63%, 84% of theory)

Sources & evidence

ORD record
ord-6732152e4436481887beab662461253d
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

Loading…