Sodium Carbonate → (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanone

HRID 1500199Notes

Reaction equation

HRID 1500199 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([C@H:10]2[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11]2)=[O:9])[CH:5]=[CH:4][CH:3]=1.[F:17][C:18]1[CH:39]=[CH:38][C:21]([O:22][C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)=[CH:20][CH:19]=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]>[CH3:15][C:12]1([CH3:16])[O:11][C@@H:10]([C:8]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:26]3[CH:25]=[CH:24][C:23]([O:22][C:21]4[CH:20]=[CH:19][C:18]([F:17])=[CH:39][CH:38]=4)=[CH:28][CH:27]=3)[N:7]=2)=[O:9])[CH2:14][O:13]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89816107(R)-(6-bromopyridin-2-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone

Product 1

HCID 89822495(R)-(2,2-dimethyl-1,3-dioxolan-4-yl)(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanoneYield 79%

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 mixture of (R)-(6-bromopyridin-2-yl)(2,2-dimethyl-1,3-dioxolan-4-yl)methanone (0.574, g, 2.01, mmol) in dioxane (10, mL) was added 2-(4-(4-fluorophenoxyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.691, g, 2.20 mmol), 2M aqueous Na2CO3, (2.0, mL, 4.0, mmol), and PdCl2(dppf) (0.086, g, 0.11 mmol). The reaction vessel was flushed with argon, sealed, and heated at 100° C. for 3, hours. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 5-40% EtOAc in hexanes. The product fractions were evaporated in vacuo to give (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanone as a very pale tan thick oil (0.621, g, 1.58, mmol, 79% yield). LC/MS: m/z=394.2, [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 5-40% EtOAc in hexanes
  6. customThe product fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-6b7d5cbe2dc64973b23761debe3fb77f
Source dataset
uspto-grants-2015_12
Patent number
US09206127B2

Reaction notes

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