Water → HCID 68825037, compound

HRID 1788397Notes

Reaction equation

HRID 1788397 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:19]1[C:23]2C=CC=CC=2N=N1.Cl.CN[O:31][CH3:32].O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11](=[CH:14][C:15](=[O:17])[NH:19][CH2:23][O:31][CH3:32])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 10681562(1-Boc-4-piperidinylidene)acetic acid

Product 1

HCID 68825037HCID 68825037, compoundYield 60.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An aqueous solution of 1 M sodium hydroxide (15 mL) was added to a solution of 3.02 g (11.8 mmol) of tert-butyl ester of 4-metoxycarbonylmethylenepiperidine-1-carboxylic acid in THF (15 mL) and stirred for 2 hours. Then an aqueous solution of 1 M sodium hydroxide (another 10 mL) was added thereto, and stirred for 18 hours. After the reaction was completed, the reaction mixture was neutralized by addition of 1 M hydrochloric acid and the solvent was removed under a reduced pressure. The residue was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. The solvent was removed under a reduced pressure to obtain 2.78 g of tert-butyl ester of 4-carboxymethylenepiperidine-1-carboxylic acid. To a solution of 2.78 g of this 4-carboxymethylenepiperidine-1-carboxylic acid tert-butyl ester in N,N-dimethylformamide (35 mL) was added 3.8 mL (34.6 mmol) of N-methylmolpholine, 2.34 g (17.3 mmol) of 1-hydroxybenzotriazole, 2.65 g (13.8 mmol) of 1-ethyl-3-(3′-dimethylaminopopyl)carbodiimide hydrochloride and 1.35 g (13.8 mmol) of N,O-dimethylhydroxylamine hydrochloride, and stirred for about 20 hours. After the reaction was completed, water was added to the reaction mixture, followed by extraction with ethyl acetate. The extract was washed with saturated brine twice and dried over anhydrous magnesium sulfate, and the solvent was removed under a reduced pressure. Its purification by silica gel column chromatography (developing solvent, hexane:ethyl acetate=3:2 to 1:1) gave 1.99 g (7.00 mmol) of 4-[(methoxymethylcarbamoyl)methylene]piperidine-1-carboxylic acid tert-butyl ester. Its physical property is shown below.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extract was washed with saturated brine twice
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed under a reduced pressure
  5. customIts purification by silica gel column chromatography (developing solvent, hexane:ethyl acetate=3:2 to 1:1)

Sources & evidence

ORD record
ord-d7c66406cc374ffb8b548acd13078612
Source dataset
uspto-grants-2009_03
Patent number
US07511144B2

Reaction notes

Loading…