1,2-Dichloroethane → HCID 69937942, compound

HRID 1058328Notes

Reaction equation

HRID 1058328 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=1[CH2:12][NH:13][C:14](=[O:20])[C@@H:15]1[CH2:19][CH2:18][CH2:17][NH:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:26]1([CH:32]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][C:34](O)=[O:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1C=C2N=NN(O)C2=CC=1.O.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=1[CH2:12][NH:13][C:14](=[O:20])[C@@H:15]1[CH2:19][CH2:18][CH2:17][N:16]1[C:34](=[O:35])[CH2:33][CH:32]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 64798Diphenylpropionic acidHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 11428605L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amide

Product 1

HCID 69937942HCID 69937942, compoundYield 105.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amide (0.030 g, 0.082 mmol), 3,3-diphenylpropanoic acid (20 mg, 0.090 mmol), and HOBT hydrate (13 mg, 0.098 mmol) in DMF (1 mL) was added EDC (0.023 g, 0.122 mmol). Diisopropylethylamine (0.0142 mL, 0.082 mmol) was added and the mixture was stirred at ambient temperature for 3 hours, at which time HPLC analysis indicated complete consumption of the proline starting material. The DMF was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and 1N HCl. The EtOAc layer was separated, washed with water, 10% aqueous Na2CO3 and brine, dried over anhydrous MgSO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue was purified by chromatography on a 10 g ISCO column using 10-100% EtOAc/hexanes over 40 min. The product-containing fractions were combined and the solvents were removed under reduced pressure to give N-(2-{[(tert-butoxycarbonyl)amino]methyl}-5-chlorobenzyl)-1-(3,3-diphenylpropanoyl)-L-prolinamide as an oil (0.050 g, 99%). HPLC RT=2.9 min, Method B; LC-MS M+H=576, 578.

Workup

  1. customconsumption of the proline starting material
  2. customThe DMF was removed under reduced pressure
  3. customthe residue was partitioned between EtOAc (50 mL) and 1N HCl
  4. customThe EtOAc layer was separated
  5. washwashed with water, 10% aqueous Na2CO3 and brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe filtrate solvent was removed under reduced pressure
  9. customthe residue was purified by chromatography on a 10 g ISCO column
  10. customover 40 min
  11. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-0962754c423f45a3a1d52b8fb1b83bac
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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