Ammonia → tert-Butyl 4-carbamoyl-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1359487Notes

Reaction equation

HRID 1359487 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O[N:19]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N>C(Cl)(Cl)Cl.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14](=[O:16])[NH2:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 177817901-((Tert-butoxy)carbonyl)-1,2,3,6-tetrahydropyridine-4-carboxylic acid

Product 1

HCID 22482730tert-Butyl 4-carbamoyl-3,6-dihydropyridine-1(2H)-carboxylateYield 25.6%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

In a mixed solution of 400 ml of chloroform and 100 ml of dimethylformamide, 20.0 g of 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridine-4-carboxylic acid was dissolved, and 14.2 g of 1-hydroxybenzotriazole hydrate and 17.7 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added thereto. The reaction mixture was stirred for 40 minutes at room temperature. The reaction solution was ice-cooled, and subsequently, 5.6 ml of 28% aqueous ammonia was added thereto, followed by stirring for 6 hours. The reaction mixture was warmed up to room temperature, and was concentrated under reduced pressure. A 5% aqueous solution of potassium hydrogensulfate was poured thereinto. The reaction mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brines, 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 5.1 g of 1-tert-butoxycarbonyl-4-carbamoyl-1,2,3,6-tetrahydropyridine as a crystal.

Workup

  1. temperaturecooled
  2. stirringby stirring for 6 hours
  3. temperatureThe reaction mixture was warmed up to room temperature
  4. concentrationwas concentrated under reduced pressure
  5. additionA 5% aqueous solution of potassium hydrogensulfate was poured
  6. extractionThe reaction mixture was extracted with ethyl acetate
  7. washThe extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brines
  8. dry with materialwas then dried over anhydrous sodium sulfate
  9. filtrationAfter the desiccant was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=1:2)

Sources & evidence

ORD record
ord-ab6e11a30a754e89a6efdcebb31b75bc
Source dataset
uspto-grants-2003_07
Patent number
US06600038B1

Reaction notes

Loading…