1,2-Dichloroethane → N-Acetyl-D-thioproline L-tyrosine methyl ester

HRID 2289416Notes

Reaction equation

HRID 2289416 reaction equation
C(Cl)CCl.[C:5]([N:8]1[CH2:15][S:14][CH2:13][C@@H:9]1[C:10]([OH:12])=[O:11])(=[O:7])[CH3:6].[CH3:16][O:17][C:18](=[O:29])[C@H:19]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[NH2:20].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[C:5]([N:8]1[CH2:15][S:14][CH2:13][C@@H:9]1[C:10]([OH:12])=[O:11])(=[O:7])[CH3:6].[CH3:16][O:17][C:18](=[O:29])[C@H:19]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=1)[NH2:20]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 70652Tyrosine Methyl EsterHCID 757711-HydroxybenzotriazoleHCID 749158(4S)-3-acetyl-1,3-thiazolidine-4-carboxylic acid

Product 1

HCID 131721907N-Acetyl-D-thioproline L-tyrosine methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (2.11 g, 11 mmol) was added to a stirred solution of N-acetyl-D-thioproline (1.75 g, 10 mmol), tyrosine methyl ester (2.32 g, 10 mmol), HOBT (1.49 g, 11 mmol) and NMM (2.31 ml, 21 mmol) in DMF (50 ml) at 0°. The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue dissolved in ethyl acetate (400 ml), and water (50 ml). The organic phase was washed with 10% citric acid (100 ml), saturated aqueous NaHCO3 (100 ml), water (100 ml) and brine (100 ml), dried (Na2SO4) and evaporated in vacuo to give the title compound as a slightly yellow powdery solid (2.75 g, 78%), used without further purification. A small portion was crystallised from EtOAC to give a white microcrystalline solid, m.p. 189-190°. δH (DMSO-D6, 400K) 7.7 (1H, br s, CONH), 6.98 (2H, d, J 8.6 Hz, ArH), 6.69 (2H, d, J 8.5 Hz, ArH), 4.83 (1H, dd, J 3.9, 7.4 Hz, CHαthiopro), 4.77 (1H, d, J 9.2 NCHAHBS), 4.53 (1H, dt, J 5.8, 8.1 Hz, CHαtyr), 4.38 (1H, d, J 9.2 Hz, NCHAHBS), 3.65 (3H, s, C O2HC), 3.25 (1H, dd, J 7.3, 11.5 Hz, CHCHAHBS), 3.05-2.97 (2H, m, CHAHBAr+CHCHAHBS), 2.89 (1H, dd, J 8.2, 14.1 Hz, CHAHBAr) and 1.99 (3H, s, CH3CO) [phenolic OH not observed at 400K, for δH (DMSO-d6, 300K) 9.19 (1H, br s, ArOH)]; m/z ESI, 27V), 353 (M+ +1).

Workup

  1. customThe DMF was evaporated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (400 ml)
  3. washThe organic phase was washed with 10% citric acid (100 ml), saturated aqueous NaHCO3 (100 ml), water (100 ml) and brine (100 ml)
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-80d25a6336b34cd8a9997ed424a2ac2c
Source dataset
uspto-grants-2000_07
Patent number
US06093696

Reaction notes

Loading…