Dimethylformamide → Nalpha-benzyloxycarbonyl-L-glutaminyl-L-tryptophan methyl ester

HRID 867033

Reaction equation

HRID 867033 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:18]([OH:20])=O)[CH2:13][CH2:14][C:15](=[O:17])[NH2:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:22][O:23][C:24](=[O:37])[C@H:25]([CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)[NH2:26].CN(C)C=O.C1(OP(N=[N+]=[N-])(=O)OC2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C>[CH3:22][O:23][C:24](=[O:37])[C@H:25]([CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)[NH:26][C:18](=[O:20])[C@H:12]([CH2:13][CH2:14][C:15](=[O:17])[NH2:16])[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

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 75855L-Glutamine, N2-[(phenylmethoxy)carbonyl]-HCID 123414Diphenylphosphoryl azideHCID 2734891Methyl tryptophanate hydrochloride

Product 1

HCID 54382161Nalpha-benzyloxycarbonyl-L-glutaminyl-L-tryptophan methyl ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a stirred mixture of Nα -benzyloxycarbonyl-L-glutamine, 56 g., and L-tryptophan methyl ester hydrochloride, 56 g., in 300 ml. of dimethylformamide at 5° C. is added diphenylphosphorazidate, 47.5 ml., in 100 ml. of dimethylformamide dropwise over ten minutes followed by 61.6 ml. of triethylamine over one hour. The mixture is stirred in an ice bath for three hours and at room temperature for 18 hours. After evaporation the residue is dissolved in 1 l. of ethyl acetate and washed successively with 500 ml. of 1N hydrogen chloride solution, 500 ml. of a saturated solution of sodium bicarbonate and 500 ml. water. The ethyl acetate layer is separated, dried, evaporated and 74.2 g. of Nα -benzyloxycarbonyl-L-glutaminyl-L-tryptophan methyl ester is obtained by recrystallization from methanol; m.p. 197°-198° C.

Workup

  1. customAfter evaporation the residue
  2. dissolutionis dissolved in 1 l
  3. washof ethyl acetate and washed successively with 500 ml
  4. customThe ethyl acetate layer is separated
  5. customdried
  6. customevaporated

Sources & evidence

ORD record
ord-9376b45e89e64d1881ccf64f84b8f763
Source dataset
uspto-grants-1978_07
Patent number
US04101538

Linked notes

Loading…