Ethyl Acetate → 2-Cyclopropyl-6-(1,3-dioxolan-2-yl)pyridine

HRID 1432417Notes

Reaction equation

HRID 1432417 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.Br[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[N:8]=1.CCOC(C)=O.[Cl-].[NH4+]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([CH:13]3[O:14][CH2:15][CH2:16][O:17]3)[N:8]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 1186132-Bromo-6-(1,3-dioxolan-2-yl)pyridineHCID 178418630HCID 178418630, compound

Product 1

HCID 193617732-Cyclopropyl-6-(1,3-dioxolan-2-yl)pyridineYield 61%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ZnCl2 in THF (0.5 M, 25 mL) was added dropwise a solution of cyclopropylmagnesium bromide (0.5 M, 25 mL) at −78° C. under nitrogen. The reaction mixture was then allowed to warm up to room temperature and stirred for an hour. The above mixture was then transferred to a sealed tube with 2-bromo-6-[1,3]dioxolan-2-yl-pyridine (1.9 g, 8.25 mmole, see subpart (a) above) and Pd(PPh3)4 (0.4 g, 0.35 mmole). TLC showed major formation of the product and some starting material. The mixture was then heated to 120° C. for 2 hours and cooled down to room temperature and then worked up with EtOAc and saturated ammonium chloride and dried over MgSO4. The residue from concentration was purified on silica gel column with 5% EtOAc in CH2Cl2 to yield 2-cyclopropyl-6-[1,3]dioxolan-2-yl-pyridine as a bright yellow liquid (0.96 g, 61%).

Workup

  1. temperatureThe mixture was then heated to 120° C. for 2 hours
  2. temperaturecooled down to room temperature
  3. dry with materialdried over MgSO4
  4. concentrationThe residue from concentration
  5. customwas purified on silica gel column with 5% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-550cc7ef812e4bffad5cf1cbefd0fde2
Source dataset
uspto-grants-2009_11
Patent number
US07612094B2

Reaction notes

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