1,2-Dichloroethane → HCID 68724495, compound

HRID 2381034Notes

Reaction equation

HRID 2381034 reaction equation
[Cl-].[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C@H:17]([NH3+:22])[C:18]([O:20][CH3:21])=[O:19])=[CH:12][C:11]=1[O:23][C:24](=[O:27])[NH:25][CH3:26])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH2:35]([O:42][C:43]([NH:45][C@@H:46]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[C:53]([O:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[CH:52]=1)[C:47](O)=[O:48])=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl>[CH3:21][O:20][C:18](=[O:19])[C@@H:17]([NH:22][C:47](=[O:48])[C@@H:46]([NH:45][C:43]([O:42][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:44])[CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH2:58][C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)=[C:53]([O:65][CH2:66][C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)[CH:52]=1)[CH2:16][C:13]1[CH:14]=[CH:15][C:10]([O:9][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[C:11]([O:23][C:24](=[O:27])[NH:25][CH3:26])[CH:12]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 46934821HCID 46934821, compoundHCID 86643600HCID 86643600, compound

Product 1

HCID 68724495HCID 68724495, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-(4-Benzyloxy-3-methylcarbamoyloxy-phenyl)-1-methoxycarbonyl-ethyl-ammonium chloride (0.2 g, 0.506 mmol) was suspended in dichloromethane (20 ml), then triethylamine (0.068 g, 0.678 mmol) was added, followed by the addition of (S)-2-benzyloxycarbonylamino-3-(3,4-bis-benzyloxy-phenyl)-propionic acid (0.31 g, 0.678 mmol) [see German patent DE 2121187] and HOBt (0.092 g, 0.678 mmol). The mixture was stirred at room temperature for 20 min. EDC (0.130 g, 0.678 mmol) was added. The stirring was continued overnight. The mixture was washed with sodium bicarbonate, dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel chromatography eluting with ethyl acetate/dichloromethane (1:2). (S)-2-[(S)-2-benzyloxycarbonylamino-3-(3,4-bis-benzyloxy-phenyl)-propionylamino]-3-(4-benzyloxy-3-methylcarbamoyloxy-phenyl)-propionic acid methyl ester was obtained as a white solid, 0.43 g. 1H NMR (400 MHz, CDCl3) 2.62 (d, J=4.6 Hz, 3H), 2.88-3.00 (m, 3H), 3.35 (s, 1H), 3.56 (s, 3H), 4.24-4.30 (m, 1H), 4.43-4.49 (m, 1H), 4.95 (m, 2H), 5.06 (m, 6H), 6.80 (m, 1H), 6.92-7.09 (m, 5H), 7.23-7.45 (m, 21H), 7.59 (m, 1H), 8.46 (d, J=7.3 Hz, 1H).

Workup

  1. waitThe stirring was continued overnight
  2. washThe mixture was washed with sodium bicarbonate
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of the solvent
  5. customthe residue was purified by silica gel chromatography
  6. washeluting with ethyl acetate/dichloromethane (1:2)

Sources & evidence

ORD record
ord-3ad49e30acc3413b96bbfbce9bd5439c
Source dataset
uspto-grants-2012_09
Patent number
US08258097B2

Reaction notes

Loading…