4-Methylmorpholine → H-Gly-Asp(OBzl)-Val-OBzl

HRID 1376687Notes

Reaction equation

HRID 1376687 reaction equation
[NH2:1][C@H:2]([C:14]([NH:16][C@H:17]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.FC(C(O)=O)(F)F.[NH:38](C(OC(C)(C)C)=O)[CH2:39][C:40](ON1C(=O)CCC1=O)=[O:41].CN1CCOCC1>C(OCC)(=O)C>[NH2:38][CH2:39][C:40]([NH:1][C@H:2]([C:14]([NH:16][C@H:17]([C:21]([O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:3][C:4](=[O:13])[O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:41]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 76926N-(tert-Butyloxycarbonyl)glycine N-hydroxysuccinimide esterHCID 131720167H-Asp(OBzl)-Val-OBzl.TFA

Product 1

HCID 131720165H-Gly-Asp(OBzl)-Val-OBzl

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 4.2 g. of H-Asp(OBzl)-Val-OBzl.TFA in 50 ml of ethyl acetate is treated in succession with 2.72 g of Boc-Gly-OSu and 0.88 ml of N-methylmorpholine and then stirred at 20° C. for 72 hours. The reaction mixture is partitioned between ethyl acetate and water and the organic phase is washed with 5% KHSO4 /10% K2SO4 solution, water, saturated NaHCO3 solution, water and saturated NaCl solution. After drying the solution is concentrated. The residue is dissolved in 30 ml of trifluoroacetic acid held at 20° C. for 20 minutes and then concentrated. After crystallization from ethyl acetate/hexane there are obtained 3.5 g of H-Gly-Asp(OBzl)-Val-OBzl, TFA (1:1), m.p. 150°-151° C.

Workup

  1. customThe reaction mixture is partitioned between ethyl acetate and water
  2. washthe organic phase is washed with 5% KHSO4 /10% K2SO4 solution, water, saturated NaHCO3 solution, water and saturated NaCl solution
  3. customAfter drying the solution
  4. concentrationis concentrated
  5. dissolutionThe residue is dissolved in 30 ml of trifluoroacetic acid
  6. waitheld at 20° C. for 20 minutes
  7. concentrationconcentrated
  8. customAfter crystallization from ethyl acetate/hexane there

Sources & evidence

ORD record
ord-0619bf1890e8441487c3a96f4ce9cd74
Source dataset
uspto-grants-1997_09
Patent number
US05663297

Reaction notes

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