4-Methylmorpholine → HCID 178501380, compound

HRID 2268801Notes

Reaction equation

HRID 2268801 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:24])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])=[CH:10][CH:9]=1)[NH2:6].[SH:25][C:26]1[N:34]=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](O)=[O:29].CN1CCOCC1>CN(C=O)C>[CH3:2][O:3][C:4](=[O:24])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:15][C:16]2[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])=[CH:12][CH:13]=1)[NH:6][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][CH:33]=[N:34][C:26]=1[SH:25]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 69806827HCID 69806827, compoundHCID 178524460HCID 178524460, compound

Product 1

HCID 178501380HCID 178501380, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of O-(2,6dichlorobenzyl)-L-tyrosine methyl ester hydrochloride (2.50 g, 6.4 mmol), 2-mercaptonicotinic acid (0.99 g, 6.4 mmol) and NMM (1.41 ml, 1.29 g, 12.8 mmol) in DMF (10 ml) was stirred at room temperature for 64 h. Solvent was removed in vacuo and the residue partitioned between DCM (30 ml) and water (25 ml). The aqueous layer was extracted with DCM (30 ml) and the combined organic layers were washed with 10% NaHCO3 solution (30 ml), dried over MgSO4 and the solvent removed in vacuo to give a brown oil which was purified by chromatography (SiO2; gradient elution, 4:1 EtOAc/hexane to 100% EtOAc) to give the title compound as a yellow foam, (2.92 g, 93%). δH (CDCl3) 8.71 (1H, dd, J 1.8, 7.6Hz), 8.05 (1H, s), 7.61 (1H, dd, J 1.8, 6.1 Hz), 7.35 (2H, m), 7.33-7.19 (2H, m), 6.94 (2H, d, J 8.7Hz), 5.22 (2H, s), 4.97 (1H, m), 3.74 (3H, s) and 3.21 (2H, m).

Workup

  1. customSolvent was removed in vacuo
  2. customthe residue partitioned between DCM (30 ml) and water (25 ml)
  3. extractionThe aqueous layer was extracted with DCM (30 ml)
  4. washthe combined organic layers were washed with 10% NaHCO3 solution (30 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent removed in vacuo
  7. customto give a brown oil which
  8. customwas purified by chromatography (SiO2; gradient elution, 4:1 EtOAc/hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-9eb107e6a3854fcdb45b2041f0372392
Source dataset
uspto-grants-2001_12
Patent number
US06329372B1

Reaction notes

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