4-Methylmorpholine → HCID 18597312, compound

HRID 1589304Notes

Reaction equation

HRID 1589304 reaction equation
[CH2:1]([O:8][C:9](=[O:16])[C@H:10]([CH2:12][CH:13]([CH3:15])[CH3:14])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:18]([CH3:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20].CN1CCOCC1>CC#N>[CH2:1]([O:8][C:9](=[O:16])[C@H:10]([CH2:12][CH:13]([CH3:14])[CH3:15])[NH:11][C@@H:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 79040Ethyl 2-bromopropionateHCID 6451313Benzyl L-leucinate

Product 1

HCID 18597312HCID 18597312, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

L-Leucine benzyl ester (186.65 g, 0.843M), ethyl 2-bromopropionate (153.1 g, 0.846M) and N-methylmorpholine (165 ml, 1.5M) were dissolved in dry CH3CN (800 ml) and refluxed for 12 h. The solvent was removed in vacuo and the residue partitioned between H2O (21) and EtOAc (3×11). The organic phase was washed with brine, dried and evaporated in vacuo. The resulting oil was chromatographed on SiO2 in 7.5% EtOAc in hexane to give the title compound (70 g) as the faster running fraction; (Found: C,67.02; H,8.42; N,4.25; C18H27NO4 requires C,67.26; H,8.47; N,4.36); νmax film 1730 cm-1 ; δ (CDCl3) 0.88 and 0.9 (each 3H, each d, each J=6.5 Hz, CH(CH3)2) 1.23 (3H,t,J=7 Hz,CH3CH2O), 1.27 (3H,d,J=7 Hz,CH3CH), 1.5 (2H,m,CHCH2), 1.7 (1H, heptet, J=7 Hz, CH(CH3)2), 2.2 (1H, br s,NH), 3.32 (2H,m, CHNHCH), 4.10 and 4.12 (each 1H, each q, each J=7 Hz, OCH2CH3), 5.12 (2H,s, OCH2C6H5) and 7.34 (5H,s, C6H5); m/e 322 (100%; [m+1])+, 260 (15), 186 (26) and 112 (28).

Workup

  1. temperaturerefluxed for 12 h
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between H2O (21) and EtOAc (3×11)
  4. washThe organic phase was washed with brine
  5. customdried
  6. customevaporated in vacuo
  7. customThe resulting oil was chromatographed on SiO2 in 7.5% EtOAc in hexane

Sources & evidence

ORD record
ord-0adf83a87c304a95943b5a86ab35787e
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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