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

HRID 2276816Notes

Reaction equation

HRID 2276816 reaction equation
Cl[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:17]=[CH2:18])[N:3]=1.[F:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)=[CH:22][CH:21]=1.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]>[F:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[CH:30]=[CH:29][C:28]([C:2]3[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:17]=[CH2:18])[N:3]=3)=[CH:27][CH:26]=2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89579914(S)-methyl 2-(2-chloro-6-vinylpyrimidine-4-carboxamido)propanoate

Product 1

HCID 89580052(S)-methyl 2-(2(4-(4-fluorophenoxy)phenyl)-6-vinylpyrimidine-4-carboxamido)propanoateYield 44%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-methyl 2-(2-chloro-6-vinylpyrimidine-4-carboxamido)propanoate (0.444 g, 1.65 mmol) in dioxane (10 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.521 g, 1.66 mmol), 2M aqueous Na2CO3 (1.65 mL, 3.30 mmol), and PdCl2(dppf) (0.071 g, 0.087 mmol). The reaction vessel was flushed with argon, sealed and heated at 100° C. overnight. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 10-40% EtOAc in hexanes. The product fractions were evaporated in vacuo to give (S)-methyl 2-(2(4-(4-fluorophenoxy)phenyl)-6-vinylpyrimidine-4-carboxamido)propanoate as a tan-yellow oil (0.304 g, 0.72 mmol, 44% yield). LC/MS: m/z=422.2 [M+H]+.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo
  5. customthe residue chromatographed over silica gel with 10-40% EtOAc in hexanes
  6. customThe product fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-73852e9c02fd4d7186ef3ed8de166c1e
Source dataset
uspto-grants-2015_09
Patent number
US09133131B2

Reaction notes

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