Sodium Hydroxide → 1-Boc-1,2,5,6-tetrahydropyridine-3-carboxylic acid

HRID 2182062Notes

Reaction equation

HRID 2182062 reaction equation
[C:1]([N:8]1[CH2:13][C:12]([C:14]([O:16]CC)=[O:15])=[CH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH-].[Na+].S([O-])(O)(=O)=O.[K+]>C(O)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][C:12]([C:14]([OH:16])=[O:15])=[CH:11][CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 113798301-Tert-butyl 3-ethyl 1,2,5,6-tetrahydropyridine-1,3-dicarboxylate

Product 1

HCID 130325691-Boc-1,2,5,6-tetrahydropyridine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In 5 ml of ethanol, 2.5 g of N-Boc-5-ethoxycarbonyl-1,2,3,6-tetrahydropyridine was dissolved, and 10 ml of a 1M aqueous solution of sodium hydroxide was added thereto. The reaction mixture was stirred for 4 hours at room temperature, and subsequently, a 5% aqueous solution of potassium hydrogensulfate was added thereto for acidification. The reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and was subsequently dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure to yield crystals of crude 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine-5-carboxylic acid The obtained crude 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine-5-carboxylic acid was dissolved in a mixed solution of 15 ml of chloroform and 2 ml of dimethylformamide, and subsequently, 1.6 g of 1-hydroxybenzotriazole hydrate and 2.0 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added thereto. The reaction mixture was stirred for 30 minutes at room temperature, and was subsequently ice-cooled. 28% aqueous ammonia in an amount of 0.64 ml was added thereto, and the reaction mixture was stirred for 1 hour. The reaction mixture was warmed up to room temperature, and subsequently concentrated under reduced pressure. A 5% aqueous solution of potassium hydrogencarbonate was poured thereinto. The reaction mixture was extracted with ethyl acetate. The extract was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, and was then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:2) to yield 1.4 g of 1-tert-butoxycarbonyl-5-carbamoyl-1,2,3,6-tetrahydropyridine as a crystal.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialwas subsequently dried over anhydrous sodium sulfate
  4. filtrationAfter the desiccant was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-14977ce8843e4a2a966cf745bc64ee75
Source dataset
uspto-grants-2005_05
Patent number
US06894168B2

Reaction notes

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