Sodium Carbonate → (S)-methyl 2-(2-chloro-6-vinylpyrimidine-4-carboxamido)propanoate

HRID 2276815Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:10][C@@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])=[O:9])[CH:5]=[C:4](Cl)[N:3]=1.[CH3:18][C:19]1(C)C(C)(C)OB(C=C)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:10][C@@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])=[O:9])[CH:5]=[C:4]([CH:18]=[CH2:19])[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of (S)-methyl 2-(2,6-dichloropyrimidine-4-carboxamido)propanoate (0.921 g, 3.31 mmol) in dioxane (10 mL) was added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.65 mL, 3.8 mmol), Na2CO3 (0,704 g, 6.64 mmol), and PdCl2(dppf) (0.142 g, 0.17 mmol). The reaction vessel was flushed with argon, sealed, and heated at 80° C. overnight. Additional 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.65 mL, 3.8 mmol) was added. After 7 hours at 80° C., additional 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.65 mL, 3.8 mmol) was added. After stirring at 80° C. for 4 more days the reaction was concentrated in vacuo to a residue and chromatographed over silica gel using 0-70% EtOAc in hexanes. The product fractions were evaporated in vacuo to give (S)-methyl 2-(2-chloro-6-vinylpyrimidine-4-carboxamido)propanoate as a yellow oil (0.444 g, 1.65 mmol, 50% yield). LC/MS: m/z=270.2 [M+H]+.

Workup

customThe reaction vessel was flushed with argon
customsealed
concentrationwas concentrated in vacuo to a residue
customchromatographed over silica gel using 0-70% EtOAc in hexanes
customThe product fractions were evaporated in vacuo

Sources & evidence

ORD record: ord-b1c723dd9cfc4d58a42967a63e74e22a
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133131B2

Reaction notes

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