p-Toluenesulfonic acid → Boc-Pro-Gly-Gly-Gly-OCH2Ph

HRID 1246736Notes

Reaction equation

HRID 1246736 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][CH2:17][C:18]([NH:20][CH2:21][C:22]([NH:24][CH2:25][C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:23])=[O:19].CC1C=CC(S(O)(=O)=O)=CC=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CCN(CC)CC>[N:8]1([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([NH:16][CH2:17][C:18]([NH:20][CH2:21][C:22]([NH:24][CH2:25][C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])=[O:23])=[O:19])=[O:12]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15431793Gly-Gly-Gly-OCH2Ph

Product 1

HCID 131726008Boc-Pro-Gly-Gly-Gly-OCH2Ph

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A solution of Boc-L-Proline (1.43 g, 6.7 mmol) and Gly-Gly-Gly-OCH2Ph.TsOH (3.0 g, 6.7 mmol) in CH2Cl2 (40 mL) and Et3N (2.80 mL) was cooled to 5° C. and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (1.34 g, 7.0 mmol) was added. The reaction was stirred at ambient temperature for 3 days and then the solvent was evaporated. The crude material was dissolved in ethyl acetate (50 mL) and washed with saturated aqueous NH4Cl (25 mL), brine (25 mL), dried over MgSO4, and then evaporated to dryness. The product was purified by column chromatography (SiO2, CH2Cl2-MeOH 95:5) to give Boc-Pro-Gly-Gly-Gly-OCH2Ph (SEQ ID NO.: 1) (2.25 g, 71%) as colorless crystals, mp 54–55° C. 1H-NMR (300 MHz, δ, CDCl3): 1.42 (9H, s), 1.80–2.20 (4H, m), 3.35–3.55 (2H, m), 3.85–4.20 (7H, m), 5.15 (2H, s), 7.05 (2H, bs), 7.30–7.35 (5H, m), 7.80 (1H, bs). 13C-NMR (75 MHz, δ, CDCl3): 24.6, 28.3, 29.4, 41.1, 43.0, 43.3, 47.2, 60.7, 66.9, 80.9, 128.4, 128.5, 128.7, 135.4, 155.8, 169.6, 170.0, 173.9. IR (KBr, cm−1):, 1753(CO), 1667(CO).

Workup

  1. customthe solvent was evaporated
  2. dissolutionThe crude material was dissolved in ethyl acetate (50 mL)
  3. washwashed with saturated aqueous NH4Cl (25 mL), brine (25 mL)
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was purified by column chromatography (SiO2, CH2Cl2-MeOH 95:5)

Sources & evidence

ORD record
ord-6d6296b4216a4d3dafde9b9be2b99036
Source dataset
uspto-grants-2006_10
Patent number
US07129208B2

Reaction notes

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