Cesium carbonate → Methyl 5-(3,3-difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylate

HRID 625020Notes

Reaction equation

HRID 625020 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:12]([O:14][CH3:15])=[O:13])=[N:6][C:7]=1[O:8][CH2:9][CH2:10][F:11].Cl.[F:17][C:18]1([F:22])[CH2:21][NH:20][CH2:19]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][C:18]1([F:22])[CH2:21][N:20]([C:2]2[CH:3]=[CH:4][C:5]([C:12]([O:14][CH3:15])=[O:13])=[N:6][C:7]=2[O:8][CH2:9][CH2:10][F:11])[CH2:19]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 90203715Methyl 5-bromo-6-(2-fluoroethoxyl)pyridine-2-carboxylate

Product 1

HCID 90203373Methyl 5-(3,3-difluoroazetidin-1-yl)-6-(2-fluoroethoxyl)pyridine-2-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

In analogy to the procedure described in Example 1 a), methyl 5-bromo-6-(2-fluoroethoxyl)pyridine-2-carboxylate (Example 147 a, 130 mg, 467 μmol) was reacted with 3,3-difluoroazetidine hydrochloride (CAN 288315-03-7, 66.6 mg, 514 μmol) in the presence of palladium (II) acetate, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and cesium carbonate to give the title compound (73 mg, 54%) as light yellow solid, MS (ESI) m/e=291.1 [MH+].

Sources & evidence

ORD record
ord-6b756355f19544089354ff4378501184
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

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