1,2-Dichloroethane → HCID 10503917, compound

HRID 1379598Notes

Reaction equation

HRID 1379598 reaction equation
[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:14]([OH:16])=[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.[Cl:24][C:25]([Cl:29])([Cl:28])[CH2:26]O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:14]([O:16][CH2:26][C:25]([Cl:29])([Cl:28])[Cl:24])=[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

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 8259TrichloroethanolHCID 1581888N-tert-Butoxycarbonyl-L-aspartic acid beta-benzyl ester2×

Product 1

HCID 10503917HCID 10503917, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Synthesis of the peptide segment is started by making the trichloroethanol ester of Boc-Asp(OBzl)-OH (Shioiri et al., 1989). This is achieved by stirring 1 g (3 mmol) of Boc-Asp(OBzl)-OH (Sigma), 0.4 ml of (3 mmol) 2,2,2-trichloroethanol (Aldrich), 100 mg of DMAP (dimethylaminopyridine; Aldrich), and 576 mg (3 mmol) of EDC (Aldrich) in 50 ml of DCM for 3 h at 0° C. and for 20 h at room temperature. The precipitate is filtered out and the filtrate is diluted with 100 ml of ethyl acetate. The ethyl acetate solution is extracted with 10% aqueous citric acid, water, saturated NaHCO3, water and saturated brine. Then, the ethyl acetate layer is dried over anhydrous Na2 SO4, decanted, and concentrated to give an oil. The crude oily product is purified by washing with petroleum ether to give Boc-Asp(OBzl)-OTce (9). 1H-NMR (CDCl3): 1.45 (9H, s), 2.93 and 3.15 (2H, dd, J=17 Hz and 4.5 Hz), 4.67 and 4.75 (2H, dd, J=12.3 Hz), 4.7-4.75 (1H, m), 5.13 (2H, s), 5.56 (1H, d, J=9 Hz), 7.34 -7.38 (5H, m). FABMS: 454 (M+1)

Workup

  1. filtrationThe precipitate is filtered out
  2. additionthe filtrate is diluted with 100 ml of ethyl acetate
  3. extractionThe ethyl acetate solution is extracted with 10% aqueous citric acid, water, saturated NaHCO3, water and saturated brine
  4. dry with materialThen, the ethyl acetate layer is dried over anhydrous Na2 SO4
  5. customdecanted
  6. concentrationconcentrated
  7. customto give an oil
  8. customThe crude oily product is purified
  9. washby washing with petroleum ether

Sources & evidence

ORD record
ord-ec814f4d6160411b83c547cce043ca36
Source dataset
uspto-grants-1997_09
Patent number
US05672584

Reaction notes

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