4-Methylmorpholine → HCID 86740025, compound

HRID 1980839Notes

Reaction equation

HRID 1980839 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][CH2:12][CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:17]([NH:21][C:22](=[O:26])[C@H:23]([CH3:25])[NH2:24])[CH2:18][CH2:19][CH3:20].C1CCC(N=C=NC2CCCCC2)CC1.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>C(Cl)Cl>[CH2:17]([NH:21][C:22](=[O:26])[C@H:23]([CH3:25])[NH:24][C:14](=[O:16])[C@H:9]([CH2:10][CH2:11][CH2:12][CH3:13])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:18][CH2:19][CH3:20]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733747N-tert-Butoxycarbonyl-L-norleucineHCID 22690439N-Butyl-L-alaninamide

Product 1

HCID 86740025HCID 86740025, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tertiarybutoxycarbonyl-L-norleucine (13.2 g) in CH2Cl2 (200 ml) was treated at 0° with L-alanine N-butylamide (5.25 g), DCC (7.77 g) and 1-hydroxybenzotriazole (5 g). The pH of the reaction mixture was adjusted to 7 with N-methyl morpholine and allowed to warm to room temperature overnight. The precipitated urea was filtered off and the filtrate washed successively with saturated aqueous sodium hydrogen carbonate, water and 1M citric acid. The organic phase was dried over sodium sulphate and the solvent evaporated in vacuo. The residue was chromatographed on silica in a gradient of 30-70% ethyl acetate in dichloromethane. Elution with 50% ethyl acetate in dichloromethane afforded the title compound (7.6 g) which crystallised from ethyl acetate as needles m.p. 108°-112°; (Found: C,60.8; H,9.8; N,11.8. C18H35N3O4 requires C,60.5; H,9.9; N,11.75%); νmax (Nujol) 3280, 3340 1675 and 1640 cms-1 δ (CDCl3) 0.9 and 0.91 (each 3H, each t, each J=5 Hz,2xCH3); 1.1-1.9 (10H,m,(CH 2)3 and (CH2)2); 1.38 (3H,d,J=5 Hz,6H2CHCH3); 1.44 (9H,s, C(CH3)3); 3.24 (2H,tt,J=5 Hz NHCH2) and 4.1 and 4.48 (each 1H, each m, 2x CH).

Workup

  1. filtrationThe precipitated urea was filtered off
  2. washthe filtrate washed successively with saturated aqueous sodium hydrogen carbonate, water and 1M citric acid
  3. dry with materialThe organic phase was dried over sodium sulphate
  4. customthe solvent evaporated in vacuo
  5. customThe residue was chromatographed on silica in a gradient of 30-70% ethyl acetate in dichloromethane
  6. washElution with 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-3451c0cb97bb477a89fafb2e745fa6ea
Source dataset
uspto-grants-1985_04
Patent number
US04511504

Reaction notes

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