4-Methylmorpholine → HCID 86752893, compound

HRID 1955677Notes

Reaction equation

HRID 1955677 reaction equation
C([N:8]([C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C@H:9]([C:11]([OH:13])=O)[CH3:10])(OC(C)(C)C)=O.C[N:25]1CCOCC1.ClC(OCC(C)C)=O.N[C@@H:40]([CH2:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)/[CH:41]=[CH:42]/[S:43]([C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=1)(=[O:45])=[O:44].Cl.O1CCOCC1>C1COCC1.C(OCC)(=O)C.C(Cl)Cl.CCOCC>[CH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:22]=[CH:23][C:14]=1[NH:8][C@H:9]([C:11]([C@@H:40]([CH2:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)/[CH:41]=[C:42](\[NH2:25])/[S:43]([C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=1)(=[O:45])=[O:44])=[O:13])[CH3:10]

Participants

10

Reactant 5

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 10360604HCID 10360604, compoundHCID 18633805HCID 18633805, compoundHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 86752893HCID 86752893, compoundYield 99%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Boc-2-naphthylalanine (2.68 g, 8.51 mmol, (Synthetech, Oregon) in THF (50 mL) at -10° C. were added 4-methylmorpholine (0.936 mL, 8.51 mmol) and isobutyl chloroformate (1.103 mL, 8.51 mmol). The mixture was stirred for 5 minutes, whereupon (S)-(E)-3-amino-5-phenyl-1-(2-naphthylsulfonyl)-1-pentene (3.30 g, 8.51 mmol) was added, followed by 4-methylmorpholine (0.936 mL, 8.51 mmol). The mixture was stirred for 45 minutes, diluted with ethyl acetate (100 mL), washed with 1M HCl (50 mL), saturated aqueous sodium bicarbonate (50 mL), and brine (50 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The intermediate, (S)-(E)-3-(tert-butoxycarbonyl-2-naphthylalanyl)amino-5-phenyl-1-(2-naphthylsulfonyl)-1-pentene, was crystallized from a suitable mixture CH2 Cl2 /ether/hexane in 69% yield. The resulting material (3.83 g, 5.90 mmol) was dissolved in CH2Cl2 (5 mL) and was treated with HCl/dioxane (15 mL of a 4.0M solution. The mixture was stirred at room temperature for 1 hour. The solution was poured, with stirring, into ether (500 mL) and filtered. The solids were washed with ether (2×50 mL) and dried in vacuo to give the intermediate, (S)-(E)-3-(2-naphthylalanyl)-amino-5-phenyl-1-(2-naphthylsulfonyl)-1-pentene, 3.41 g, 99% yield.

Workup

  1. additionwas added
  2. washwashed with 1M HCl (50 mL), saturated aqueous sodium bicarbonate (50 mL), and brine (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe intermediate, (S)-(E)-3-(tert-butoxycarbonyl-2-naphthylalanyl)amino-5-phenyl-1-(2-naphthylsulfonyl)-1-pentene, was crystallized from a suitable mixture CH2 Cl2 /ether/hexane in 69% yield
  7. stirringThe mixture was stirred at room temperature for 1 hour
  8. additionThe solution was poured
  9. filtrationfiltered
  10. washThe solids were washed with ether (2×50 mL)
  11. customdried in vacuo

Sources & evidence

ORD record
ord-a3763809bdc6415dbbf30e9b8d703393
Source dataset
uspto-grants-1998_07
Patent number
US05776718

Reaction notes

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