Hydrogen Bromide → Benzyloxycarbonylseryl-asparaginyl-phenylalanine methyl ester

HRID 986350Notes

Reaction equation

HRID 986350 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:15]([OH:17])=O)[CH2:13][OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1CCCCC1)C.C(Cl)(=O)C(C)(C)C.[CH3:33][O:34][C:35](=[O:53])[C@H:36]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[NH:37][C:38](=[O:45])[C@H:39]([CH2:41][C:42](=[O:44])[NH2:43])[NH2:40].Br>ClCCl.N1C=CC=CC=1>[CH3:33][O:34][C:35](=[O:53])[C@H:36]([CH2:46][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[NH:37][C:38](=[O:45])[C@H:39]([CH2:41][C:42](=[O:44])[NH2:43])[NH:40][C:15](=[O:17])[C@H:12]([CH2:13][OH:14])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 13007N-Ethylpiperidine2×HCID 62493Pivaloyl chlorideHCID 100310N-(Benzyloxycarbonyl)-L-serineHCID 15567215Asparaginyl-phenylalanine methyl ester

Product 1

HCID 14369384Benzyloxycarbonylseryl-asparaginyl-phenylalanine methyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Benzyloxycarbonylserine (8.4 g; 35 mmoles), N-ethylpiperidine (4.9 ml) and pyridine (3.5 ml) in dichlormethane (100 ml) cooled to -20° C. are treated under constant stirring with pivaloylchloride (4.4 ml); the mixture is stirred and cooled (0° C.) a further 8 minutes. After that, within 2 to 3 minutes, a solution of asparaginyl-phenylalanine methyl ester, liberated from its hydrobromide (13.1 g; 35 mmoles) by the addition of N-ethylpiperidine (4.9 ml), in dichloromethane (100 ml) is added. The reaction mixture is stirred for 2 hours at room temperature and evaporated. The noncrystalline residue is dissolved in ethyl acetate and the solution is successively washed with 1 M hydrochloric acid, water, 5% sodium hydrogencarbonate and water, dried over anhydrous sodium sulfate, and evaporated, after which the residue is crystallized from methanol. The yield is 9.1 g (51%), m.p. 180°-183° C. A sample is recrystallized from the same solvent and has m.p. 184°-186° C. Rf 0.71/S1, 0.82/S2. [α]D20 -13.8° (c 0.2; methanol). Composition: C25H30N4O8.

Workup

  1. additionare treated
  2. additionis added
  3. stirringThe reaction mixture is stirred for 2 hours at room temperature
  4. customevaporated
  5. dissolutionThe noncrystalline residue is dissolved in ethyl acetate
  6. washthe solution is successively washed with 1 M hydrochloric acid, water, 5% sodium hydrogencarbonate and water
  7. dry with materialdried over anhydrous sodium sulfate
  8. customevaporated
  9. customafter which the residue is crystallized from methanol
  10. customA sample is recrystallized from the same solvent

Sources & evidence

ORD record
ord-3cae27cb189c4981a05d1d9e0265cc24
Source dataset
uspto-grants-1987_12
Patent number
US04711952

Reaction notes

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