1,2-Dichloroethane → N-Acetyl-D-thioproline L-tyrosine tert.butyl ester

HRID 2289415Notes

Reaction equation

HRID 2289415 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].[C:16]([O:20][C:21](=[O:32])[C@H:22]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[NH2:23])([CH3:19])([CH3:18])[CH3:17].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].[C:16]([O:20][C:21](=[O:32])[C@H:22]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[NH2:23])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 749158(4S)-3-acetyl-1,3-thiazolidine-4-carboxylic acidHCID 6950582L-Tyrosine 1,1-dimethylethyl ester

Product 1

HCID 131721906N-Acetyl-D-thioproline L-tyrosine tert.butyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (4.22 g, 22 mmol) was added to a solution of N-acetyl-D-thioproline (3.50 g, 20 mmol), tyrosine tert.butyl ester (4.74 g, 20 mmol), HOBT (2.97 g, 22 mmol) and NMM (2.42 ml, 22 mmol) in DMF (80 ml) at 0°. The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue dissolved in ethyl acetate (600 ml) and water (50 ml). The organic phase was washed with 10% citric acid (150 ml), saturated aqueous NaHCO3 (150 ml), water (150 ml) and brine (150 ml), dried (Na2SO4) and evaporated in vacuo to give the title compound as an off-white solid (7.39 g, 94%); δH (DMSO-d6, 300K) (2 rotameric species observed) 9.17 (1H, br s, ArCH), 8.43 (3, J 8.0 Hz), and 8.09 (d, J 8.0 Hz) together (1H, CONH), 6.98 (2H, t, J 7.6, ArH), 6.64 (2H, d, J 7.3, ArH), 4.81-4.67 (m), 4.47 (d, J 8.7 Hz) and 4.35-4.21 (m), together (4H, CHα-tyr, CHαthiopro and NCH2S), 3.32 (dd, J 7.2, 11.6 Hz), 3.17 (dd, J 7.5, 11.6 Hz), 2.99-2.72 (m) together (4H, CH2Ar+CHCH2S), 2.06 (s) and 1.84 (s) together (3H, CH3CO) and 1.36 (9H, S, CO2tBu); m/z (ESI, 15V) 395 (M+ +1).

Workup

  1. customThe DMF was evaporated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (600 ml)
  3. washThe organic phase was washed with 10% citric acid (150 ml), saturated aqueous NaHCO3 (150 ml), water (150 ml) and brine (150 ml)
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-e9dbb68f3f0c49e49e9619cb5dfe9adb
Source dataset
uspto-grants-2000_07
Patent number
US06093696

Reaction notes

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