4-Methylmorpholine → HCID 54193900, compound

HRID 2269824Notes

Reaction equation

HRID 2269824 reaction equation
[Br:1][C@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=O.Cl.[NH2:14][CH:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:16]([O:18][CH2:19][CH3:20])=[O:17].CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C.CCCCCC.O1CCCC1>[Br:1][C@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([NH:14][CH:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:5]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 11746403(R)-2-Bromo-3-phenylpropionic acid

Product 1

HCID 54193900HCID 54193900, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent3×

Procedure

Combine (R)-2-bromo-3-phenylpropionic acid (3.44 g, 15 mmol), diethyl aminomalonate hydrochloride (4.23 g, 20 mmol), and N-methylmorpholine (5.5 mL, 50 mmol) in dichloromethane (50 mL). Add 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloric acid salt (3.83 g, 20 mmol) and 1-hydroxybenztriazole hydrate (2.70 g, 20 mmol). Add tetrahydrofuran (10 mL). After 20 hours, concentrate in vacuo and partition the concentrated reaction mixture between an aqueous 5% sulfuric acid solution and methyl t-butyl ether. Separate the layers and extract the organic layer with a saturated aqueous sodium bicarbonate solution and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 1/4 ethyl acetate/hexane, 1/3 ethyl acetate/hexane, and then 2.5/1 ethyl acetate/hexane to give diethyl 2-((R)-2-bromo-3-phenylpropionylamino)malonate.

Workup

  1. concentrationconcentrate in vacuo
  2. custompartition
  3. customthe concentrated reaction mixture between an aqueous 5% sulfuric acid solution and methyl t-butyl ether
  4. customSeparate the layers
  5. extractionextract the organic layer with a saturated aqueous sodium bicarbonate solution
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. customevaporate in vacuo
  9. customto give a residue

Sources & evidence

ORD record
ord-01eba57df7714c94b7b475d99bdb242b
Source dataset
uspto-grants-2001_12
Patent number
US06329550B1

Reaction notes

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