1,2-Dichloroethane → HCID 69939790, compound

HRID 1058225Notes

Reaction equation

HRID 1058225 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:12]=1[CH2:13][NH:14][C:15](=[O:21])[C@@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH2:27].ON1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2N=N1.[CH2:38](Cl)[CH2:39]Cl.CCN(C(C)C)C(C)C.CN([CH:54]=[O:55])C>>[OH:27][C@@:38]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([CH3:39])[C:54]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:16]1[C:15]([NH:14][CH2:13][C:12]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:11]=1[CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:21])=[O:55]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 23560073HCID 23560073, compound

Product 1

HCID 69939790HCID 69939790, compound

Procedure

To a solution of L-prolin-N-(2-(2-(tert-butyloxycarbonylamino)ethyl)-5-chlorobenzyl)amide (0.50 g, 1.31 mmol), 1-hydroxybenzotriazole hydrate (0.215 g, 1.4), and 2R-hydroxy-2-phenylpropionic acid (0.215 g, 1.3 mmol) in DMF (15 mL) was added EDC (0.29 g, 1.5 mmol). To the stirred solution was added DIEA (approximately 0.14 mL) until the solution measured pH 6 on wetted E. Merck pH indicator strips. The mixture was stirred for 18 h at ambient temperature. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (100 mL) and saturated aqueous sodium bicarbonate solution (50 mL). The organic phase was separated, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography using 98:2 CH2Cl2:MeOH as eluant. The product-containing fractions were combined and removal of the solvent under reduced pressure gave 1-((2R)-2-hydroxy-2-phenylpropanoyl)-N-(2-(2-(tert-butyloxycarbonylamino)ethyl)-5-chlorobenzyl)-L-prolinamide as a gum (0.62 g; TLC Rf=0.3 (98:2 CH2Cl2:MeOH); HPLC RT=3.46 min, method A; LC-MS m/z=530).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between EtOAc (100 mL) and saturated aqueous sodium bicarbonate solution (50 mL)
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash silica gel column chromatography
  8. customremoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-e695aff4b28443d482b1c3138cf9ac52
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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