1,2-Dichloroethane → N-Acetyl-D-thioproline (O-benzyl)-L-tyrosine methyl ester

HRID 2289421Notes

Reaction equation

HRID 2289421 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].Cl.[CH3:17][O:18][C:19](=[O:37])[C@H:20]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:25][CH:24]=1)[NH2:21].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(Cl)Cl>[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].[CH3:17][O:18][C:19](=[O:37])[C@H:20]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[CH:25][CH:24]=1)[NH2:21]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 749158(4S)-3-acetyl-1,3-thiazolidine-4-carboxylic acidHCID 12616037H-Tyr(Bzl)-OMe.HCl

Product 1

HCID 131721909N-Acetyl-D-thioproline (O-benzyl)-L-tyrosine methyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

EDC (211 mg, 1.1 mmol) was added to a stirred solution of N-acetyl-D-thioproline (175 mg, 1 mmol), O-benzyl tyrosine methyl ester hydrochloride (322 mg, 1 mmol), HOBT (149 mg, 1.1 mmol) and NMM (242 μl, 2.2 mmol) in DCM (10 ml) at 0°. The mixture was stirred at room temperature overnight then diluted with DCM (100 ml). The DCM solution was washed with 1M hydrochloric acid (30 ml), saturated aqueous NaHCO3 (30 ml) and water (30 ml), dried (Na2SO4) and evaporated in vacuo. The residue was purified by chromatography (SiO2 ; ethyl acetate) to give the title compound as a white foam (417 mg, 94%); δH (DMSO-d6, 300K) (2 rotameric species observed) 8.55 (d. J 7.8 Hz) and 8.28 (3, J 8.1 Hz) together (1H, NHCO), 7.43-7.25 (5H, m, Ph), 7.14-7.08 (2H, m, ArH), 6.92-6.88 (2H, m, ArH), 5.06 (2H, s, CH2Ph), 4.79-4.66 (m) and 4.45-4.42 (m) and 4.21 (d, J 9.7 Hz) together (4H, CHα-tyr, CHα-thiopro and NCH2S), 3.62 (s) and 3.61 (s) together (3H, CO2Me), 3.28-2.71 (4H, m, CHCH2Ar+CHCH2S) and 2.04 (s) and 1.82 (s) togher (3H, CH3CO); m/z (ESI, 15V) 443 (M+ +1).

Workup

  1. washThe DCM solution was washed with 1M hydrochloric acid (30 ml), saturated aqueous NaHCO3 (30 ml) and water (30 ml)
  2. dry with materialdried (Na2SO4)
  3. customevaporated in vacuo
  4. customThe residue was purified by chromatography (SiO2 ; ethyl acetate)

Sources & evidence

ORD record
ord-428946c4cdfc4df7928fcaa6d572c43f
Source dataset
uspto-grants-2000_07
Patent number
US06093696

Reaction notes

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