4-Methylmorpholine → N-(1-{3-(1-benzyloxycarbonyl-4-piperidyl)propionyl}-1,2,3,4-tetrahydro-3-quinolylcarbonyl]-beta-alanine ethyl ester

HRID 843735Notes

Reaction equation

HRID 843735 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH2:37]([O:39][C:40](=[O:56])[CH2:41][CH2:42][NH:43][C:44]([CH:46]1[CH2:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[NH:48][CH2:47]1)=[O:45])[CH3:38]>CN(C)C=O.O1CCCC1.O>[CH2:37]([O:39][C:40](=[O:56])[CH2:41][CH2:42][NH:43][C:44]([CH:46]1[CH2:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[N:48]([C:19](=[O:21])[CH2:18][CH2:17][CH:14]2[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:10])[CH2:16][CH2:15]2)[CH2:47]1)=[O:45])[CH3:38]

Participants

8

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 98953153-(1-((Benzyloxy)carbonyl)piperidin-4-yl)propanoic acidHCID 22611816N-[(1,2,3,4tetrahydro-3-quinolyl)carbonyl]-beta-alanine ethyl ester

Product 1

HCID 22611879N-(1-{3-(1-benzyloxycarbonyl-4-piperidyl)propionyl}-1,2,3,4-tetrahydro-3-quinolylcarbonyl]-beta-alanine ethyl esterYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of 3-(1-benzyloxycarbonyl-4-piperidyl)propionic acid (0.18 g) in N,N-dimethylformamide (3 ml) was added N-methylmorpholine (0.09 ml) and isobutylchloroformate (0.1 ml) under stirring at −15° C. After stirring at −15° C. for 2 hours, N-[(1,2,3,4-tetrahydro-3-quinolyl)carbonyl]-β-alanine ethyl ester (0.22 g) and N-methylmorpholine (0.12 ml) in tetrahydrofuran (2 ml) was added. After stirring at 0° C. for 2 hours and ambient temperature for overnight, the mixture was poured into water, and extracted with ethyl acetate. The extract was washed with 5% KHSO4 aqueous solution saturated NaHCO3 aqueous solution and brine, and dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel eluting with (CHCl3:MeOH=100:1) to give N-[1-{3-(1-benzyloxycarbonyl-4-piperidyl)propionyl}-1,2,3,4-tetrahydro-3-quinolylcarbonyl]-β-alanine ethyl ester as an oil (0.18 g).

Workup

  1. stirringAfter stirring at −15° C. for 2 hours
  2. stirringAfter stirring at 0° C. for 2 hours and ambient temperature for overnight
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with 5% KHSO4 aqueous solution saturated NaHCO3 aqueous solution and brine
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo
  7. customThe residue was purified by chromatography on silica gel eluting with (CHCl3:MeOH=100:1)

Sources & evidence

ORD record
ord-8ca09cbf61eb49af85e684eb8e5d4b61
Source dataset
uspto-grants-2002_04
Patent number
US06380215B1

Reaction notes

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