1,2-Dichloroethane → HCID 131722408, compound

HRID 1530932Notes

Reaction equation

HRID 1530932 reaction equation
CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[C:18]([N:25]1[CH2:32][S:31][CH2:30][C@@H:26]1[C:27]([OH:29])=[O:28])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(Cl)CCl.Cl.[CH3:38][O:39][C:40](=[O:51])[C@H:41]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([OH:50])=[CH:46][CH:45]=1)[NH2:42]>CN(C=O)C>[C:18]([N:25]1[CH2:32][S:31][CH2:30][C@@H:26]1[C:27]([OH:29])=[O:28])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[CH3:38][O:39][C:40](=[O:51])[C@H:41]([CH2:43][C:44]1[CH:45]=[CH:46][C:47]([OH:50])=[CH:48][CH:49]=1)[NH2:42]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 76956Methyl tyrosinate hydrochlorideHCID 688406BOC-D-THZ-OH

Product 1

HCID 131722408HCID 131722408, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NMM (0.39 g, 0.43 ml, 3.9 mmol), HOBT (0.57 g, 4.2 mmol), Boc-D-thioproline (0.91 g, 3.9 mmol), and EDC (0.75 g, 3.9 mmol) were added sequentially to a stirred solution of L-tyrosine methyl ester hydrochloride (0.82 g, 3.5 mmol) in dry DMF (10 ml). The reaction mixture was stirred at room temperature for 0.75 h. The DMF was removed in vacuo and the residue partitioned between EtOAc (70 ml) and 10% aqueous Na2CO3 (30 ml). The phases were separated and the aqueous phase re-extracted with EtOAc (2×20 ml). The combined organic extracts were washed with brine (10 ml), dried (Na2SO4) and evaporated in vacuo to afford the crude product as a viscous oil. Purification by flash chromatography (SiO2; 5:95 MeOH/DCM) afforded the title compound as a white solid (1.1 g, 76%): 6H (CDCl3) 6.96 (2 H, d, J 8.5 Hz, ArH), 6.85 (1 H, br s NH), 6.72 (2 H, d, J 8.5 Hz, ArH), 5.95 (1 H. br s, OH), 4.81 (1 H, apparent dt, J 5.8, 8 Hz, CHα-tyr), 4.73 (1 H, br s, CHα-thiopro), 4.63 (1 H, br d, J 9.0 Hz, NCHAHBS), 4.28 (1 H, d, J 9.0 Hz, NCHAHBS), 3.71 (3 H, s, CO2CH3), 3.37-3.28 (1 H, br m, CHCHAHBS), 3.21-3.10 (1 H, m, CHCHAHBS), 3.09-2.97 (2 H, m, CH2Ar), and1.45 (9 H, s, tBu); m/z (ESI, 27 V) 411 (MH+).

Workup

  1. customThe DMF was removed in vacuo
  2. customthe residue partitioned between EtOAc (70 ml) and 10% aqueous Na2CO3 (30 ml)
  3. customThe phases were separated
  4. extractionthe aqueous phase re-extracted with EtOAc (2×20 ml)
  5. washThe combined organic extracts were washed with brine (10 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customto afford the crude product as a viscous oil
  9. customPurification by flash chromatography (SiO2; 5:95 MeOH/DCM)

Sources & evidence

ORD record
ord-eefeebc85cae40be9beeb2d88737bc59
Source dataset
uspto-grants-2001_03
Patent number
US06197794B1

Reaction notes

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