Ammonium Chloride → Ethyl 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylate

HRID 2206262Notes

Reaction equation

HRID 2206262 reaction equation
[CH2:1]([N:8]([CH2:16][C:17]([F:24])([F:23])[C:18]([O:20]CC)=O)[CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[Cl-].[NH4+]>C1COCC1>[CH2:1]([N:8]1[CH2:16][C:17]([F:23])([F:24])[C:18]([OH:20])=[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 59442745Ethyl 3-(benzyl(3-ethoxy-3-oxopropyl)amino)-2,2-difluoropropanoate

Product 1

HCID 67343743Ethyl 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylateYield 126.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl N-benzyl-N-(3-ethoxy-2,2-difluoro-3-oxopropyl)-β-alaninate (25.0 g) in anhydrous THF (200 mL) was added dropwise lithium diisopropylamide (2M, 72.8 mL) at −78° C. The reaction mixture was stirred at room temperature for 2 hr, and added to saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (27.4 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f263252858d04d3fae7b487e51cbd375
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

Loading…