1,2-Dichloroethane → HCID 58281374, compound

HRID 1475288Notes

Reaction equation

HRID 1475288 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C@H:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:5].C(Cl)CCl.[NH:19]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:20]([C:23](O)=[O:24])[CH2:21][CH3:22].CN(C=O)C>C(Cl)Cl.N(C(OC(C)(C)C)=O)[C@H](C(O)=O)CC>[CH3:1][O:2][C:3](=[O:14])[C@H:4]([N:6]([CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:23](=[O:24])[C@@H:20]([NH:19][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH3:22])[CH3:5]

Participants

7

Reactant 4

HCID 111,2-Dichloroethane2×HCID 6228DimethylformamideHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 10987118methyl (2R)-2-(benzylamino)propanoate

Product 1

HCID 58281374HCID 58281374, compoundYield 87.6%

Reagents, catalysts & solvents 2

HCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-benzylamino-propionic acid methyl ester (3.5 g, 18.1 mmol) and EDC (3.65 g, 19.0 mmol) in anhydrous DCM (30 mL) was added Boc-Abu-OH (3.68 g, 18.1 mmol). The reaction was stirred for 18 h, then additional Boc-Abu-OH (0.74 mmol, 3.62 mmol), EDC (1.35 g 7.1 mmol) and DMF (2.4 mL) were added to the reaction, followed by stirring for 18 h. The solvent was removed in vacuo and the resulting oil was dissolved in EtOAc (50 mL) and washed with 1 M hydrochloric acid (50 mL×3), 1 M aqueous NaOH (50 mL×3), brine (50 mL), dried over sodium sulfate, filtered and concentrated, to give (R)-2-[benzyl-((S)-2-tert-butoxycarbonylamino-butyryl)-amino]-propionic acid methyl ester (6.0 g, 87%) as a pale colourless oil. An aliquot (3.9 g, 10.3 mmol) was dissolved in DCM (52 mL) and HCl gas was bubbled through the reaction for 30 min at ambient temperature. The reaction was stirred for an additional hour and then solvent removed in vacuo. The resultant solid was triturated with Et2O, to give (R)-2-[((S)-2-amino-butyryl)-benzyl-amino]-propionic acid methyl ester hydrochloride (3.0 g, 93%) as a colourless solid. This material was slurried in EtOAc (47 mL) at ambient temperature and saturated aqueous sodium bicarbonate (14 mL) added. After stirring for 18 h, the organic layer was separated and washed with brine, dried over sodium sulfate, filtered and concentrated, to give the title compound (1.68 g, 72%) as a colourless oil. 1H NMR (Me-d3-OD): 7.44-7.23 (5H, m), 5.19 (1H, d), 4.28-4.08 (2H, m), 3.86 (1H, q), 2.18-1.99 (1H, m), 1.96-1.79 (1H, m), 1.46 (3H, d), 0.95 (3H, t).

Workup

  1. stirringby stirring for 18 h
  2. customThe solvent was removed in vacuo
  3. dissolutionthe resulting oil was dissolved in EtOAc (50 mL)
  4. washwashed with 1 M hydrochloric acid (50 mL×3), 1 M aqueous NaOH (50 mL×3), brine (50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-12d2b0b8a26840f095c9033f2b77e0ca
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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