4-Methylmorpholine → Boc-Gly-Ala-Pro-OBzl

HRID 260248Notes

Reaction equation

HRID 260248 reaction equation
[NH:1]([C:21]([O:23]C(C)(C)C)=O)[C@H:2]([C:4]([N:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])=[O:5])[CH3:3].[NH:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29]C(O)=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1>Cl.O1CCOCC1.CN(C=O)C>[NH:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][C:21]([NH:1][C@H:2]([C:4]([N:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9])=[O:5])[CH3:3])=[O:23]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 13068139N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester

Product 1

HCID 14656486Boc-Gly-Ala-Pro-OBzlYield 87.9%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

Boc-Ala-Pro-OBzl (75.3 g, 0.2 mole) was deprotected by stirring for 1.5 h. in 4.2 N HCl in dioxane. Excess HCl and dioxane were removed under reduced pressure, triturated with ether, faltered, washed with ether, and dried (yield 100%). A solution of Boc-Gly-OH (35.04 g, 0.2 mole) and HOBt (27.02 g, 0.2 mole) in DMF was cooled to -15° C. with stirring and EDCI (38.34 g, 0.2 mole) was added. After 20 rain, a pre-cooled solution containing the above hydrochloride salt and NMM (21.98 mL, 0.2 mole) was added and the reaction mixture was stirred overnight at room temperature. The mixture was evaporated to a thick oil which was dissolved in CHCl3. This solution was extracted with water, 10% citric acid, water, 5 % NaHCO3, water, and dried over Na2SO4. The solvent was removed under reduced pressure and the resulting oil was crystallized from ether/petroleum ether. The solid was filtered, washed with petroleum ether, and dried to obtain 76.2 g (yield 87.88%) of II. R1f 0.39; R2f, 0.44.

Workup

  1. customExcess HCl and dioxane were removed under reduced pressure
  2. customtriturated with ether
  3. washwashed with ether
  4. customdried (yield 100%)
  5. additionwas added
  6. stirringthe reaction mixture was stirred overnight at room temperature
  7. customThe mixture was evaporated to a thick oil which
  8. dissolutionwas dissolved in CHCl3
  9. extractionThis solution was extracted with water, 10% citric acid, water, 5 % NaHCO3, water
  10. dry with materialdried over Na2SO4
  11. customThe solvent was removed under reduced pressure
  12. customthe resulting oil was crystallized from ether/petroleum ether
  13. filtrationThe solid was filtered
  14. washwashed with petroleum ether
  15. customdried

Sources & evidence

ORD record
ord-4bfb2ae552f84c4bb379337040a71e88
Source dataset
uspto-grants-1996_06
Patent number
US05527610

Reaction notes

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