4-Methylmorpholine → HCID 73933413, compound

HRID 1587592Notes

Reaction equation

HRID 1587592 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6].[OH2:15].[OH:16][C:17]1[C:25]2[N:24]=NN[C:21]=2[CH:20]=[CH:19][CH:18]=1.CN1[CH2:32][CH2:31][O:30][CH2:29]C1.CCN=C=N[CH2:38][CH2:39][CH2:40]N(C)C.Cl.CN(C)CCCN=C=N[CH2:53][CH3:54]>O1CCCC1>[C:32]1([CH2:31][O:30][C:29]([NH:24][CH2:25][CH2:21][CH2:20][CH2:19][CH2:18][C:17]([NH:6][C@H:5]([C:4]([O:3][CH3:2])=[O:14])[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:16])=[O:15])[CH:38]=[CH:39][CH:40]=[CH:54][CH:53]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 75736Methyl L-phenylalaninate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 73933413HCID 73933413, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of Z-aminocaproic acid (i.e. the title A compound) (18.6 g, 0.07), L-phenylalanine methyl ester hydrochloride (16.6 g, 0.077 mol), hydroxybenzotriazole hydrate (10.7 g, 0.07 mol) in 350 mL of dry tetrahydrofuran cooled in an ice bath was added N-methylmorpholine (7.1 g, 0.07 mol) followed by water soluble carbodiimide reagent, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (13.5 g, 0.07 mol). After stirring cold for 4 hours, the reaction was allowed to warm to ambient temperature overnight. The reaction mixture was then concentrated in vacuo and next treated with ethyl acetate (400 mL) and pH 4 phosphate buffer (200 mL). The organic phase was rinsed with saturated aqueous sodium hydrogen carbonate solution until thin layer chromatography showed the absence of Z-aminocaproic acid, then with brine and dried over anhydrous magnesium hydrate. Removal of solvents gave 28 g of crude product. This crude product was absorbed onto Baker silica gel (50 g), then flash chromatographed on Merck silica gel (400 g) eluting with 1:1 ethyl acetate:hexane. Collection of the product, eluted in yellow colored fractions, gave 23.3 g of the title B compound as a solid, m.p. 83°-85° C.

Workup

  1. temperaturecooled in an ice bath
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. additionnext treated with ethyl acetate (400 mL) and pH 4 phosphate buffer (200 mL)
  4. washThe organic phase was rinsed with saturated aqueous sodium hydrogen carbonate solution until thin layer chromatography
  5. dry with materialwith brine and dried over anhydrous magnesium hydrate
  6. customRemoval of solvents
  7. customgave 28 g of crude product
  8. customThis crude product was absorbed onto Baker silica gel (50 g)
  9. customflash chromatographed on Merck silica gel (400 g)
  10. washeluting with 1:1 ethyl acetate
  11. customCollection of the product
  12. washeluted in yellow colored fractions
  13. customgave 23.3 g of the title B compound as a solid, m.p. 83°-85° C.

Sources & evidence

ORD record
ord-78b234d4391b4983949089e411fa93b9
Source dataset
uspto-grants-1993_06
Patent number
US05217958

Reaction notes

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