Sodium Hydroxide → 4-(4-Fluoro-phenyl)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester

HRID 253076Notes

Reaction equation

HRID 253076 reaction equation
C[O:2][C:3]([C:5]1[CH2:6][N:7]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8][CH2:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=[O:4].[OH-].[Na+]>O1CCOCC1>[C:21]([O:20][C:18]([N:7]1[CH2:8][CH2:9][C:10]([C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)=[C:5]([C:3]([OH:4])=[O:2])[CH2:6]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 589858404-(4-Fluoro-phenyl)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

Product 1

HCID 533752574-(4-Fluoro-phenyl)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl esterYield 79.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-(4-fluoro-phenyl)-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (6.8 g, 20 mmol), 100 ml 1,4-dioxane and 100 ml 2 M NaOH was stirred at RT for 20 h. After extraction of the reaction mixture with two portions of tert-butyl methyl ether, the combined organic layers were extracted with 1 M aqueous sodium hydroxide solution (100 ml). The combined aqueous layers were cooled to 0° C. by addition of ice (150 g) and acidified to pH 1 with ice-cold 4 M aqueous hydrochloric acid solution (70 ml). The aqueous layer was extracted with three 150 ml-portions of ethyl acetate. The combined organic layers were washed with brine (50 ml), dried over sodium sulfate and concentrated in vacuo. Crystallization of the crude acid (6.4 g) from a mixture of n-heptane and ethyl acetate (19:1, 120 ml) gave the title compound as white crystals (5.1 g, 78%).

Workup

  1. extractionAfter extraction of the reaction mixture with two portions of tert-butyl methyl ether
  2. extractionthe combined organic layers were extracted with 1 M aqueous sodium hydroxide solution (100 ml)
  3. temperatureThe combined aqueous layers were cooled to 0° C. by addition of ice (150 g)
  4. extractionThe aqueous layer was extracted with three 150 ml-portions of ethyl acetate
  5. washThe combined organic layers were washed with brine (50 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customCrystallization of the crude acid (6.4 g)
  9. additionfrom a mixture of n-heptane and ethyl acetate (19:1, 120 ml)

Sources & evidence

ORD record
ord-1ffb5142c9e34b16b36ff84157028eb1
Source dataset
uspto-grants-2011_01
Patent number
US07872022B2

Reaction notes

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